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Review

Progress in clinical oncolytic virus-based anti-tumor therapy

LI Qian, XU Yichun, OU Ying, LI Manjing, HAN Junsong

Tumor. 2022, 42(11): 778-789. https://doi.org/10.3781/j.issn.1000-7431.2022.2206-0339

Abstract (480) Download PDF (3757)

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Oncolytic viruses (OVs) have recently become promising cancer immunotherapy agents as they specifically replicate in tumor cells and induce tumor cells death, without affecting normal cells. OVs have received more and more attention from scientific research and the biomedical industry. Herein, an overview of the definition, classification, characteristics and mechanisms of OVs, and the review of the clinical status of anti-tumor OVs which have been approved and are still in clinical trials are provided. Clinical therapeutic effects of combinatorial approach of OVs with other treatments such as chemotherapy, radiotherapy, and immunotherapy on heterogeneous tumors and tumor microenvironment are also reviewed. The clinical evaluations of these combination therapy strategies in improving drug resistance in malignant tumors are also discussed.

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Review

Research progress in allogeneic CAR-T cells

FANG Yaling, DONG Yuqian, WANG Yanan, WU Weiyi

Tumor. 2021, 41(05): 363-370. https://doi.org/10.3781/j.issn.1000-7431.2021.55.827

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Chimeric antigen receptor (CAR)-T cells have changed the therapeutic prospects of hematological malignancies. However, CAR-T cells approved for clinical use must be produced on a customized basis, which limits their large-scale clinical application. Exploring the allogeneic CAR-T cell technology that can achieve “off-the-shelf supply”, cell product standardization, multiple antigens targeting, and low industrial production cost is one of the main directions of adoptive immunotherapy. However, allogeneic CAR-T cells may cause life-threatening graft-vs-host disease (GvHD) and may be quickly cleared by the host immune system. In this paper, the progress in evading GvHD and heterologous CAR-T cell immunogenicity based on gene editing technology, and the current clinical and research on heterologous CAR-T cells are reviewed. The improved next-generation allogeneic CAR-T cells may pave the way for further breakthroughs in recurrent or refractory malignant tumors.

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Expert Views

Research progress of biological markers for immunotherapy in patients with pancreatic cancer

JIANG Anyi, LIU Yuzhi, QUAN Ming

Tumor. 2024, 44(01): 77-88. https://doi.org/10.3781/j.issn.1000-7431.2024.2305-0245

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Pancreatic cancer is one of the common gastrointestinal malignancies, the incidence of which is increasing year by year and has become one of the most important public health problems worldwide. At present, tumor treatment has entered the era of immunotherapy, but the response of pancreatic cancer patients to immune checkpoint inhibitors is not ideal. In addition, there is a lack of effective and validated biomarkers to stratify patients who may benefit from immunotherapy. This review has summarized the current research advances of immunotherapeutic biomarkers in pancreatic cancer, hoping to help clinicians understand relevant biomarkers systematically and guide the precise treatment of pancreatic cancer.

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Expert Forum

Progress in targeted therapy and immunotherapy for advanced cancer

MAO Aihong, WU Yuanyuan, WANG Jun

Tumor. 2022, 42(01): 15-23. https://doi.org/10.3781/j.issn.1000-7431.2022.2105-0333

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Thyroid cancer is the most common malignant tumor of endocrine system. Although the prognosis of most differentiated thyroid cancers is generally good and with a 10-year survival rate of more than 90%, there is still a lack of effective treatment for late recurrent, metastatic and radioactive iodine refractory thyroid cancer and anaplastic thyroid cancer. With the rapid development of molecular biology technology and the discovery of new biomarkers for thyroid cancer, which has significantly improved the understanding of the molecular pathogenesis of thyroid cancer, thus allowing more personalized treatments for patients with advanced thyroid cancer. This article reviews the current targeted therapy and immunotherapy for advanced thyroid cancer with good antitumor activity and clinical benefits, in order to improve the prognosis of patients with advanced thyroid cancer.

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Review

Research progress of C-Myc in multiple myeloma

YANG Ning, ZHONG Hua

Tumor. 2021, 41(02): 131-138. https://doi.org/10.3781/j.issn.1000-7431.2021.55.318

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Multiple myeloma (MM) is a plasma cell malignant proliferative disease characterized by the accumulation of clonal plasma cells in bone marrow. The incidence of multiple myeloma is second in hematological malignancies. C-Myc is an oncogene that high expresses abnormally in a variety of solid tumors and hematological malignancies. It has been approved that the increased expression of C-Myc is associated with poor prognosis of tumor patients. Multiple myeloma evolves from a premalignant stage named monoclonal gammopathy of undetermined significance (MGUS), followed by smoldering MM (SMM) and finally evolved to symptomatic myeloma. C-Myc deregulation is one of the key features of disease progression. Identifying the role of C-Myc in the occurrence and development of MM is important for clarifying the pathogenesis of MM and may help in developing new treatment strategies.

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Review

Advances in mechanism of sorafenib resistance in treatment of primary hepatic carcinoma

CHEN Hualei, LI Wei

Tumor. 2021, 41(06): 435-443. https://doi.org/10.3781/j.issn.1000-7431.2021.2104-0204

Abstract (415) Download PDF (2190)

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In China, targeted therapy is the standard treatment for advanced primary liver cancer. Sorafenib plays an important role in the standard targeted therapy of liver cancer, but it only has curative effect on about 30% of patients, and drug resistance usually occurs within 6 months, which limits the therapeutic effect of sorafenib. It is very important to explore the drug resistance mechanism of sorafenib and enhance its curative effect. The mechanism of sorafenib resistance may be related to the epigenetic changes of tumor cells, drug transport, changes of tumor microenvironment and hepatitis virus infection. In addition, autophagy, iron death, epithelial mesenchymal transformation of tumor cells and tumor cell activation are also research hotspots. At present, the exploration of sorafenib resistance mechanism is still in progress. On this basis, how to improve the sensitivity of patients with primary liver cancer to sorafenib is an important challenge. This paper reviews the latest research progress in sorafenib resistance in primary liver cancer, and discusses how to enhance the sensitivity of sorafenib.

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Review

Progress in application of platelet stimulating agents in management of cancer therapy-related thrombocytopenia

WANG Yanfei, LIU Wei

Tumor. 2022, 42(03): 203-212. https://doi.org/10.3781/j.issn.1000-7431.2021.2201-0046

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Cancer therapy-related thrombocytopenia (CTRT) is a common side effect during anti-cancer therapies. In this paper, the present situation of CTRT, the research progress in platelet-promoting drugs including recombinant human interleukin-11, recombinant thrombopoietin and thrombopoietin receptor agonist in the field of CTRT are reviewed, and the future clinical research direction of the treatment of CTRT with thrombopoietin drugs is prospected, so as to provide references and suggestions for better prevention and treatment of CTRT.

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Review

Extracellular matrix: biological effects on tumor development and therapy

YANG Xi , WANG Siyao , HAO Linlin , ZHANG Yining

Tumor. 2021, 41(11): 792-802. https://doi.org/10.3781/j.issn.1000-7431.2021.2106-0417

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With the advantages of good efficacy and few adverse effects, immunotherapy has gradually become a hotspot in cancer treatment. As an important part of the tumor microenvironment, the extracellular matrix (ECM) also contributes to the heterogeneity and complexity of the tumor microenvironment, which has a non negligible role in the development of cancer and the development of resistance to immunotherapy. This review will focus on the ECM in the tumor microenvironment, focusing on the key components of the ECM, such as collagens, adhesins, growth factors, proteolytic enzyme proteins, polysaccharide complexes, and glycoproteins that are important in tumor development and therapy, dissecting the mechanisms by which the ECM influences the process of tumor development and possible effective therapeutic targets with a view to tumor immunotherapyIde as are provided in.

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Review

Current status and perspectives of tumor immunotherapy efficacy evaluation methods

GE Yuchen, LIU Baorui, LI Rutian

Tumor. 2023, 43(09): 740-746. https://doi.org/10.3781/j.issn.1000-7431.2023.2212-0885

Abstract (340) Download PDF (1989)

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Tumor immunotherapeutics include immune checkpoint inhibitors, adoptive cellular therapy, tumor vaccines, immunomodulators, which regulate or induce anti-tumor activity by blocking immunosuppressive signals, infusing in vitro-induced anti-tumor effector cells, and enhancing the immunogenicity of tumor cells in the fight against cancer. The effect mechanisms of tumor immunotherapy is different from that of other tumor therapeutic approaches, such as surgery and chemotherapy. Therefore, in the evaluation of anti-tumor efficacy, the use of conventional imaging methods to detect the volume change of tumor lesions shows special response patterns such as “false progression” and “superprogression”, which cannot timely and accurately evaluate the objective efficacy of tumor immunotherapy. This review is an attempt to focus on those challenges in evaluating immunotherapy efficacy and the latest developments of relevant evaluation criteria, and is aimed at providing reference for the scientific evaluation of tumor immunotherapy efficacy and the selection of appropriate immunotherapy strategies for tumor patients.

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Review

Advances in transmembrane protein TMEM176B and its related diseases

JIANG Linlan, WANG Jiahui, XU Yi, SHEN Zan

Tumor. 2022, 42(11): 790-796. https://doi.org/10.3781/j.issn.1000-7431.2022.2202-0102

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Transmembrane protein 176B (TMEM176B), originally known as TORID, is a transmembrane protein with four potential transmembrane structural domains that are predominantly expressed in lymphoid tissue. It plays a regulatory role in dendritic cell maturation, antigen cross-presentation, and tumor cell behavior, and influences the development of diseases such as graft-versus-host disease, neurological disorders and tumors. In this paper, the structure, localization and biological functions of TMEM176B and its role in diseases are reviewed, with the aim of providing a reference for subsequent studies on the function of TMEM176B and interventions in related diseases.

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Review

Research progress in CDK4/6 inhibitors in neoadjuvant therapy of HR-positive HER2-negative breast cancer

XIAO Hongyan, ZHANG Lina, GU Lin

Tumor. 2022, 42(12): 835-844. https://doi.org/10.3781/j.issn.1000-7431.2022.2111-0864

Abstract (551) Download PDF (1964)

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Cyclin-dependent kinase (CDK)4/6 inhibitors are a new class of targeted therapeutics that block the proliferation of malignant tumor cells by inhibiting the progression of cell cycle. CDK4/6 inhibitors have been successfully used in patients with hormone receptor positive (HR﹢)/human epidermal growth factor receptor 2 negative (HER2﹣) advanced or metastatic breast cancer. CDK4/6 inhibitors combined with endocrine therapy significantly extended progression-free survival in patients with advanced stage and were well tolerated. However, its efficacy in patients with early breast cancer has not been determined. In recent years, many clinical trials have begun to explore the application prospect of CDK4/6 inhibitors in neoadjuvant therapy of early HR﹢/HER2﹣ breast cancer. In this paper, the latest clinical trials of neoadjuvant therapy with CDK4/6 inhibitors in order to improve pathologic complete response (pCR) rate and prognosis of patients with HR﹢/HER2﹣ breast cancer were reviewed.

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Review

Progress in anti-tumor therapy targeting CD47

LIU Jingjing, TANG Chenchen, LI Hui, CHENG Ying

Tumor. 2021, 41(09): 640-649. https://doi.org/10.3781/j.issn.1000-7431.2021.2102-0099

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CD47 is an immunoglobulin-like protein widely expressed on the surface of many cell membranes, and its activation can mediate cell proliferation, migration, phagocytosis and apoptosis. A variety of tumor cells highly express CD47, which binds to signal regulatory protein α (SIRPα) on the surface of macrophages and sends a "don't eat me" signal, thus evading the surveillance of macrophages and achieving the purpose of immune escape. In recent years, CD47 has become one of the hottest research spots among various targets for tumor immunotherapy, and several new drugs are under development. In this review, we described the structure and function, the anti-tumor biological effects of CD47 to provide an overview on the research status and progress of new drugs targeting CD47, as well as the prospects of clinical application in this field.

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Review

Research progress of molecular targeted therapy in intrahepatic cholangiocarcinoma

DUAN Yi, HU Suxian, YANG Xupeng, WU Zhihua, DUAN Yourong, SUN Ying

Tumor. 2022, 42(11): 750-760. https://doi.org/10.3781/j.issn.1000-7431.2022.2110-0810

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Intrahepatic cholangiocarcinoma (iCCA) is a rare gastrointestinal malignant tumor, which has an insidious onset and lacks screening methods. Molecular targeted therapy has a good therapeutic effect on this highly heterogeneous disease. Therapeutic targets that have made quite good research progress include epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and its receptor (VEGFR), isocitrate dehydrogenase (IDH), fibroblast growth factor receptor (FGFR), heat shock protein 90 (HSP90), C-ROS oncogene 1 (ROS1), etc. Among them, FGFR2 and IDH1 gene mutations are found in iCCA exclusively. Some drugs that target these targets have achieved significant clinical efficacy and approved by the administration. Gate keeper mutations are prone to emerge in the kinase domain of FGFR, resulting in the acquired drug resistance of iCCA. Drugs such as TAS-120 and HSP90 inhibitors have the prospect of reversing iCCA resistance, instead, their efficacy and safety need to be further verified in preclinical and clinical research. In this paper, the research progress of iCCA

molecular targeted therapy is reviewed, and the difficulties and solutions of iCCA targeted therapy drug resistance are discussed and prospected.

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Review

Research progress of m⁶A demethylase FTO and ALKBH5 in tumors

HE Yichen, CHEN Yimeng, WU Changping

Tumor. 2021, 41(04): 280-295. https://doi.org/10.3781/j.issn.1000-7431.2021.55.886

Abstract (473) Download PDF (1649)

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As the most common post-transcriptional modification of eukaryotic mRNA, N⁶-methyladenosine (m⁶A) has an extensive influence on alternative splicing of mRNA, 5’ and 3’ end processing, nuclear export and translation, and is involved in a variety of physiological activities. Along with the discovery of demethylase fat mass and obesity-associated protein (FTO) and AlkB homologue 5 (ALKBH5), m⁶A is considered to be dynamic and reversible. The abnormal expressions of FTO and ALKBH5 proteins in tumors often lead to the disordered m⁶A modifications, which have a significant impact on the maintenance of tumor stem cells, the proliferation, migration and invasion of tumor cells, and even the sensibility to, radiotherapy and chemotherapy. In most tumors, the abnormally expressed FTO and ALKBH5 proteins play a cancer-promoting effect, which makes the exploration on m⁶A demethylase inhibitors a research hotspot in recent years. However, since both FTO and ALKBH5 belong to the AlkB dioxygenase family and they have a conserved protein domain, it makes the development of highly specific inhibitors difficult. This article reviews the molecular mechanism and biological effects of m⁶A demethylase in various tumors, and summarizes the current research progress of m6A demethylase inhibitors, in order to comprehensively understand the possibility of m⁶A demethylase serving as a tumor diagnosis and prognosis biomarker or a key therapeutic target.

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Review

Current status and prognostic value of PD-1/PD-L1 in treatment of colorectal cancer

TIAN Ruoxi, MENG Zesong, WANG Guiying, WANG Guanglin, WANG Feifei, YAO Qingbin

Tumor. 2020, 40(03): 215-222. https://doi.org/10.3781/j.issn.1000-7431.2020.55.195

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The death rate of colorectal cancer (CRC) is the fourth in worldwide. It is an important cause of cancer-related death and seriously affects the survival and quality of life of patients. Surgery, chemotherapy and radiotherapy are the main treatments for CRC. However, the overall survival of CRC patients has not been significantly improved. So the new treatments are urgently needed. Tumor immune escape plays a key role in tumor proliferation, recurrence and metastasis. Immune checkpoints programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) play an important role in tumor immune escape. Anti-PD-1/PD-L1 therapy has become a hotspot in cancer research. More and more studies have showed anti-PD-1/PD-L1 immunotherapy has achieved remarkable efficacy in the treatment of microsatellite instability-high (MSI-H) CRC. Therefore, this paper summarizes the clinical application of anti-PD-1/PD-L1 therapy in the treatment of CRC and the various strategies to improve its low response rate. And the predictive value of PD-L1 expression on the surface of tumor cells in the prognosis of CRC is also reviewed.

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Review

Advance in clinical research of radiotherapy for primary and metastatic liver malignancies

XIAO Jie, CAO Peiguo

Tumor. 2020, 40(01): 60-67. https://doi.org/10.3781/j.issn.1000-7431.2020.55.094

Abstract (232) Download PDF (1517)

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Surgical treatment is the primary curative treatment for hepatocellular carcinoma and liver metastasis of colorectal cancer, but most patients are ineligible for the treatment upon initial diagnosis. And the overall efficacy of topical treatments such as radiofrequency ablation or transcatheter arterial chemoembolization remains limited. As an important supplementary treatment for surgery, radiotherapy plays an increasingly important role in the treatment of hepatic malignancies with the development of radiotherapy and the progress of liver cancer research. At the same time, the focus of liver radiation is on the safety of radiotherapy, especially the risk of radiation-induced liver disease. In this review, the recent advances in the clinical studies and safety of radiotherapy for hepatocellular carcinoma and liver metastasis of colorectal cancer were summarized.

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Review

Single cell sequencing technology and its application in pancreatic cancer

YAO Hongfei, YANG Jianyu, ZHANG Junfeng

Tumor. 2022, 42(11): 761-765. https://doi.org/10.3781/j.issn.1000-7431.2022.2201-0057

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Pancreatic cancer has a high degree of malignancy and a very poor clinical efficacy, and little effect has been achieved on improving the cure rate and survival rate of pancreatic cancer patients in recent years. Therefore, there is an urgent need to raise awareness of pancreatic cancer in order to help obtain more accurate disease information for personalized treatment. Traditional high throughput sequencing technology is mainly used to identify the driving genes associated with the occurrence and development of pancreatic cancer, but it ignores the tumor heterogeneity in pancreatic cancer. As an emerging technology, single cell sequencing technology can significantly make up for the shortcomings of traditional sequencing technology. Conduct in-depth exploration on the heterogeneity of malignant tumors, tumor occurrence and development, tumor resistance, and tumor treatment at different omics levels of individual cells. This review mainly summarizes the application of single cell sequencing technology in the study of pancreatic cancer.

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Review

Effect on the occurrence and development of tumor of β adrenergic receptor

LI Xiaoyan, LI Yaxing, JIA Yitao

Tumor. 2021, 41(09): 650-656. https://doi.org/10.3781/j.issn.1000-7431.2021.2010-0897

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β-adrenergic receptor (β-AR) is a G-protein coupled receptor which is expressed in a variety of tumor cells, with β2-AR being the major type of β-AR expressed in tumor cells. The interaction between catecholamine and β-AR can promote the proliferation, apoptosis, invasion and migration of tumor cells through a variety of ways, thus affecting the occurrence and development of tumor. Recent studies have found that β-AR is also widely expressed in immune cells, and can affect the tumor immune microenvironment by regulating the function of immune cells, and then affect the occurrence and development of tumors. Clinical studies have found that the expression of β-AR is closely related to the prognosis of tumor patients. β-AR blockers can not only reduce the mortality of some tumor patients, but also counteract the drug resistance of chemotherapy, improve the sensitivity of radiotherapy and cooperate with immune checkpoint inhibitors. Targeting β-AR may be a new choice for tumor therapy. This article reviews the role of β-AR in tumorigenesis and development.

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Review

Research progress on the mechanisms of tumour metastasis influenced by surgery

YANG Yuxue, JIANG Chenyu, WANG Jie, XU Jianhua, YUAN Xu, JIANG Yiming

Tumor. 2021, 41(03): 215-224. https://doi.org/10.3781/j.issn.1000-7431.2021.55.976

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Surgery is currently the main treatment for most solid malignant tumors. Accumulating evidences have shown that surgical trauma-induce stress response, inflammation, immunosuppression, pain and tissue damage, which are closely associated with the local recurrence and distant metastasis of primary tumours. Therefore, this article reviews the mechanisms and progress involved emphatically in surgery-mediated metastasis, and proposes exploiting to t provide a new idea and theoretical basis for the adjuvant drugs in the perioperative period of cancer patients. This review firstly describes the theoretical basis of operation-induced metastasis, then presents the latest clinical research progress, and finally gives an outlook for the future research on perioperative treatment.

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Review

Research progress on the relationship between liver metastasis and tumor microenvironment in colorectal cancer

HUANG Yichu, JIANG Lei

Tumor. 2024, 44(03): 241-251. https://doi.org/10.3781/j.issn.1000-7431.2024.2308-0407

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The incidence and mortality of colorectal cancer (CRC) have been increasing year by year, and liver metastasis is the main cause of death for CRC patients. Approximately 49% of CRC patients died of liver metastasis, and about 25% of them developed liver metastasis after radical resection. The interaction between various cytokines (such as chemokines, exosomes) and immune cells in the tumor microenvironment (TME) is essential for tumor metastasis. So far, the mechanism of colorectal liver metastases (CRLM) has not been fully elucidated, but some studies have shown that CRLM does not only occur in the late stage of CRC, but also in the early stage of some patients. In this paper, we summarized the current understanding of CRLM pathogenesis from genomics, pathology, and TME perspectives. And we also reviewed the latest molecular regulatory mechanisms of CRLM, as well as the mechanisms of immune cells and cytokines related to TME. Finally, the latest research findings of CRLM immunotherapy are summarized, in order to provide new insights into the comprehensive treatment for CRLM patients.

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Review

Research progress in targeted antibody-drug conjugates for HER2-positive breast cancer

DONG Yuqian, FANG Yaling, WU Weiyi, WANG Yanan

Tumor. 2021, 41(06): 444-450. https://doi.org/10.3781/j.issn.1000-7431.2021.2011-0996

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Breast cancer is the most common malignant tumor in women, and it is also the main cause of death in women. According to the breast cancer classification criteria set at the 2013 St.Gallen International Conference on Breast Cancer, breast cancer is divided into four types. Among the four types of breast cancer, human epidermal growth factor receptor type 2 (HER2) positive breast cancer accounts for 15%-20%, which is highly malignant and has a poor prognosis. In the past two decades, a variety of FDA-approved targeted drugs against HER2-positive breast cancer have come out, including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-conjugated drugs (ADC). However, with the increase in drug side effects and drug resistance, people have to develop new ADCs with less side effects and drug resistance. This article reviews the mechanism and some clinical studies of ADCs that have been put on the market and are about to be put on the market for anti-HER2 positive breast cancer.

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Review

Research progress of ferroptosis in digestive system cancers

LU Lu, GAO Xing, LI Shuanghang, YE Jiazhou, LIN Yan, LIANG Rong

Tumor. 2022, 42(04): 285-294. https://doi.org/10.3781/j.issn.1000-7431.2022.2202-0089

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Ferroptosis is a unique new form of cell death, which is characterized by iron-dependent oxidative damage, excessive accumulation of lipid peroxides and reactive oxygen species (ROS). Rapid progress has been made for understanding the roles of ferroptosis in various malignant tumors of the digestive system. As revealed by multiple research projects, cancer cell growth could be inhibited through regulating the expression of target genes that are involved in the signaling pathways of ferroptosis, highlighting the great therapeutic potential of ferroptosis regulation in tumor therapy. This review is focused on the current research progress of ferroptosis in malignant tumors of the digestive system and has summarized the roles of ferroptosis-related molecules and signaling pathways in the development of malignant tumors of the digestive system as well as the therapeutic application and research progress of ferroptosis-related drugs in the treatment of malignant tumors of the digestive system. Finally, future research directions and currently unresolved issues of ferroptosis in tumors were discussed, aiming to strengthen the theoretical basis for the important roles of ferroptosis in tumors of the digestive system from different perspectives, provide new ferroptosis-related therapeutic options for malignant tumors of the digestive system, and point out directions for further translational research.

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Expert Forum

Interpretation of the data set for reporting carcinoma of the thyroid recommended by the International Collaboration on Cancer Reporting

LIU Zhiyan, WANG Xinpei

Tumor. 2022, 42(01): 44-52. https://doi.org/10.3781/j.issn.1000-7431.2022.2105-0298

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Data set for reporting carcinoma of thyroid was summarized by the International Collaboration on Cancer Reporting (ICCR), including core elements and non-core elements. The data set uses recent World Health Organization (WHO) classification of thyroid tumors to get the clinical and prognostical nomenclature. It further highlights the importance of risk stratification according to the vascular invasion and extrathyroidal extension for the patients. It is by far the first data set to include mitotic activity and tumor necrosis as two independent parameters for reporting carcinoma of the thyroid. It further emphasizes the importance of evaluating the volume of metastasis of the lymph nodes on recurrence risk stratification. The ICCR thyroid data set help generating a report to lead a more rationale therapy and avoid incomplete therapy for lethal tumors and unnecessary treatment for indolent tumors.

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Clinical Research

Efficacy and safety of bevacizumab combined chemotherapy in metastatic breast cancer: a Meta-analysis

DU Linjuan, LIU Shuang, LI Ming, WANG Chunguang

Tumor. 2021, 41(03): 197-205. https://doi.org/10.3781/j.issn.1000-7431.2021.33.835

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Objective: To evaluate the efficacy and safety of chemotherapy plus bevacizumab versus chemotherapy alone in the treatment of advanced breast cancer systematically.

Methods: A computer-based online search was performed by using PubMed, Cochrane Library, Excerpta Medica Database (EMbase), VIP, China National Knowlege Infrastructure (CNKI) and WANFANG databases. The search time ranged from the establishment of the database to September 2020. After screening those articles and extracting data strictly, Meta-analysis was performed by RevMan 5.3. The main endpoints of this study were median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), and safety.

Results: A total of 10 articles were included, including 5 210 patients. Meta-analysis showed that the treatment of chemotherapy plus bevacizumab could effectively improve ORR [odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.56-2.05, P < 0.00 001] and mPFS [hazard ratio (HR) = 0.70, 95% CI = 0.63-0.78, P < 0.000 01] in metastatic breast cancer compared with the treatment of chemotherapy alone, but they did not show an advantage in mOS, and the difference was not statistically significant (HR = 0.94, 95% CI = 0.84-1.05, P = 0.28). In terms of safety, Grade Ⅲ and above adverse reactions, the chemotherapy plus bevacizumab group had higher rate of proteinuria (OR = 10.87, 95% CI = 4.68-25.22, P < 0.000 01), hypertension (OR = 8.39, 95% CI = 3.56-19.78, P < 0.000 01), neuropathy (OR = 1.36, 95% CI = 1.03-1.70, P = 0.03). There was no significant difference in neutropenia (OR = 1.25, 95% CI = 0.95-1.65, P = 0.11], and bleeding (OR = 1.95, 95% CI = 0.96-3.95, P = 0.07) between two groups.

Conclusion: Compared with chemotherapy alone, the combination of bevacizumab could effectively improve ORR and mPFS in patients with advanced breast cancer, but the incidence of hypertension, proteinuria, and neurotoxicity is high.

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Review

Progress in the research and theranostics of neurofibromatosis type Ⅰ

YUAN Zhiqing, YANG Tian, CHEN Tao, HUA Rong, LIU Yingbin

Tumor. 2023, 43(09): 756-762. https://doi.org/10.3781/j.issn.1000-7431.2023.2306-0272

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Neurofibromatosis type 1 is a progressive autosomal dominant inherited disease caused by a mutation in neurofibromin 1 (NF1) gene located on chromosome 17q11.2. NF1 can cause systemic peripheral neuropathy, but the clinical manifestations are varied due to the different onset times and lesion sites in different patients. The treatment of NF1 involves multiple disciplines due to different lesion sites. Clinical monitoring and symptomatic treatment are the main methods for NF1 management, while radical treatment is difficult. New drugs targeted at the pathogenic gene-related signaling pathways are expected to improve the therapeutic effect for NF1. This review summarizes the progress in the basic research and clinical diagnosis and treatment of NF1.

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Expert Commentary

Comments on concensus on clinical management of cancer therapy-related thrombocytopenia

WANG Liwei

Tumor. 2021, 41(12): 828-831. https://doi.org/10.3781/j.issn.1000-7431.2021.2112-0945

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Myelosuppression is common in tumor treatment, which can lead to serious disease burden of cancer therapy-related thrombocytopenia. Thrombocytopenia will increase the risk of bleeding, affect the intensity of tumor treatment and bring adverse effects. At present, the consensus and guidelines on chemotherapy-related thrombocytopenia have been released. The content of this consensus is expanded from the consensus on chemotherapy-related thrombocytopenia caused by various anti-tumor treatments, especially filling in the blanks of consensus and guidelines for thrombocytopenia caused by radiotherapy. This consensus covers the whole process of risk classification, diagnostic evaluation, preventive intervention, treatment and follow-up, so as to bring more comprehensive and accurate thrombocytopenia management strategy for cancer patients.

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Review

Anticancer therapy mediated by glucose oxidase

HE Xiaobo, HE Yongjing, LI Pengping, XU Xin, CHEN Bo, CAO Guodong, XIONG Maoming

Tumor. 2020, 40(02): 146-152. https://doi.org/10.3781/j.issn.1000-7431.2020.55.757

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Glucose oxidase is a kind of endogenous oxidoreductase which exists widely in organism. In recent years, due to its inherent biocompatibility, low toxicity and unique catalytic effect on beta-D-glucose, glucose oxidase has attracted more and more attention in the field of biomedicine. Glucose oxidase can effectively catalyze the oxidation of glucose into gluconic acid and hydrogen peroxide. Researchers have developed various anticancer therapies based on glucose oxidase using this catalytic property: (1) glucose consumption provides alternative treatment strategies for cancer starvation; (2) oxygen consumption increases tumor hypoxia, which can be used for tumor hypoxia activation therapy; (3) the production of gluconic acid increases the acidity of tumor microenvironment, which can trigger the release of pH-responsive drugs; (4) the production of hydrogen peroxide increases the oxidative stress level of tumors. Hydrogen peroxide can be converted into toxic hydroxyl radicals by being exposed to light (such as near-infrared light) or fenton reaction, thus killing cancer cells. In addition, glucose oxidase can also be used in combination with other biological enzymes, hypoxia-activated prodrugs, photosensitizers or fenton reagents to produce the multi-mode synergistic anticancer therapies with starvation therapy as the main part, cooperating with hypoxia-activated therapy, oxidation therapy, photodynamic therapy and light therapy, etc. In this review, the glucose oxidase-mediated tumor monotherapy is firstly introduced, and the multi-mode synergistic anti-cancer therapy mediated by glucose oxidase as well as its specific anti-tumor mechanism are systematically elaborated.

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Review

Whole-course nutrition management for patients with biliary tract cancer

XIONG Yichen, GONG Wei

Tumor. 2022, 42(08): 580-590. https://doi.org/10.3781/j.issn.1000-7431.2021.2201-0077

Abstract (228) Download PDF (1291)

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Biliary tract cancer (BTC) is a highly malignant disease with poor prognosis and is prone to recurrence and metastasis. Radical surgery in combination with comprehensive treatment measures including chemotherapy and radiotherapy is the main treatment strategy currently. Malnutrition is common in BTC patients partially due to the long treatment cycle of this disease, which often impedes the implementation of treatment and negatively affects the prognosis. Nutrition support is one of the key components of comprehensive treatment regimen throughout the whole process of BTC management. Proper evaluation and standardized whole processing nutrition management can reduce the risk of malnutrition in patients, thereby shortening the postoperative length of stay (LOS), improving the quality of life as well as clinical outcomes. This paper will elaborate on the whole-course nutrition management during BTC treatment, in order to provide further insight into the clinical application of whole-course nutritional management in the field of BTC treatment.

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Expert Forum

Robotic thyroid surgery: summary of current situation and prospect

SUN Hanxing, YAN Jiqi

Tumor. 2022, 42(01): 24-30. https://doi.org/10.3781/j.issn.1000-7431.2022.2106-0356

Abstract (271) Download PDF (1226)

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Robotic surgery system has been more and more adopted in thyroid surgery, in addition to the significant cosmetic effect, its own advantages in operability are appreciated. With the development of technology, the scope of robotic surgery has been constantly broken through, and more complex thyroid cases have been included in the research. As a high-tech surgical platform, augmented reality, artificial intelligence, machine learning and many other new technologies are integrated into thyroid surgery through robotic surgery. As a product of the combination of modern technology and traditional surgery, robotic surgery system will be more intelligent in the future, leading the development of surgery through technological change.

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Criterion and Interpretation

Interpretations and applications of ultrasound diagnostic classification systems of ACR TI-RADS, Kwak TI-RADS and Chinese-TI-RADS in the risk assessments of thyroid nodules

DU Jing

Tumor. 2021, 41(11): 733-739. https://doi.org/10.3781/j.issn.1000-7431.2021.2107-0449

Abstract (488) Download PDF (1217)

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Thyroid imaging reporting and data system (TI-RADS) is a reference basis for radiologists to perform risk stratification of thyroid nodular malignancy according to the characteristics of ultrasound images. At present, there is no unified TI-RADS over the world, and its value in thyroid nodule risk assessment and clinical practice is unclear. This paper aims to interpret and analyze clinical value of American College of Radiology (ACR) TI-RADS (2017 version), TI-RADS proposed by Jin Young Kwak (Kwak-TI-RADS) (2011 version) and Chinese TI-RADS (C-TI-RADS) (2020 version) in the risk assessment for thyroid nodules and clinical administration, in order to provide references for selecting suitable TI-RADS in clinical practice.

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Cancer Epidemiology

Progress in epidemiological studies of cancer burden, causes and research on diet, nutrients and cancer risks

TUO Jiayi, XIANG Yongbing

Tumor. 2023, 43(04): 359-366. https://doi.org/10.3781/j.issn.1000-7431.2023.2306-0275

Abstract (286) Download PDF (1202)

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Cancer is a disease with high malignancy, easy invasion and metastasis, and poor prognosis, but effective prevention and intervention measures are helpful to control its occurrence and development, and reduce its burden. The causes of cancer are complex, including external exposures to environmental risk factors, host factors, genetic susceptibility and so on. In recent years, the relationships between diet, nutrients and cancer had obtained increasing attention from the public and epidemiologists. The prevalence and external causes of cancer, as well as the research progress in nutritional epidemiology of cancer are briefly introduced in this article. Particularly, the significance in diet and nutrition on cancer prevention and the challenges in current research are discussed, in order to provide references for diet and nutrition in primary cancer prevention and public health policy-making.

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Review

Progress in the role of tumor-associated fibroblasts in esophageal squamous cell carcinoma

ZHANG Qian, LIANG Yabing, YANG Ling

Tumor. 2022, 42(04): 295-304. https://doi.org/10.3781/j.issn.1000-7431.2021.2107-0499

Abstract (321) Download PDF (1201)

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Esophageal squamous cell carcinoma (ESCC) is a type of esophageal cancer (EC) and one of the most lethal malignant tumors with poor prognosis. In addition to cancer cells, the tumor microenvironment (TME), which consists of a series of resident cells, recruited cells and extracellular matrix, is also one of the reasons for its intractability. Cancer-associated fibroblasts (CAFs) are an important group of cells existing in the tumor microenvironment. CAFs acquire an activated phenotype through binding with various cytokines such as leukemia inhibitory factor (LIF), interleukin-6 (IL-6), IL-8, C-C motif chemokine ligand 2 (CCL2), etc., secrete soluble molecules, remodel the extracellular matrix, promote tumor proliferation and growth, accelerate tumor invasion and metastasis, and induce tumor tolerance to immunity and resistance to chemotherapy. Currently, CAFs are believed to play important roles in the treatment and prognosis prediction of ES. Therefore, a better understanding of the major effects of CAFs on ESCC and the underlying molecular mechanisms will help to find more valuable therapeutic targets and guide clinical practice more effectively.

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Expert Forum

Progress and controversy of endoscopic thyroid surgery via anterior chest approach

WANG Tiantian, WANG Ping

Tumor. 2022, 42(01): 31-37. https://doi.org/10.3781/j.issn.1000-7431.2022.2105-0346

Abstract (221) Download PDF (1152)

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Since the application of totally endoscopic thyroid surgery (TET) in 1996, its characteristics of safety, effectiveness and minimally invasiveness have been continuously verified. TET via anterior chest approach is the earliest and most widely used surgical method, shared understanding has been formulated and published by Chinese experts consensus in 2017. The development of surgery has always been a tortuous process. The continuous improvement in the clinical positioning, indications, surgical scope and refined operation of TET via anterior chest approach has also been facing many controversies. In this article, the progress and controversies of TET via anterior chest approach based on the experience of The Second Affiliated Hospital of Zhejiang University College of Medicine and the related literatures were reviewed, aiming to promote the standardization and popularization of this procedure which could benefit more patients with surgical thyroid diseases.

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Expert Forum

Advances in treatment of differentiated thyroid cancer

QIAN Kai, GUO Kai, SHI Yuan, WANG Zhuoying

Tumor. 2022, 42(01): 2-7. https://doi.org/10.3781/j.issn.1000-7431.2022.2202-0108

Abstract (347) Download PDF (1071)

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The incidence rate of thyroid cancer has increased rapidly in recent years. With the deepening understanding of thyroid cancer and the development of medical technology, the treatment of thyroid cancer has been improved. At the same time, the concept of individualized, multi-disciplinary and coordinated therapy is emphasized. This article briefly describes the status and development of differentiated thyroid cancer treatment in recent years from four aspects: endoscopic operation, active surveillance, neoadjuvant therapy and targeted therapy.

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Review

From basic to clinical: Advances in research on ETV1

QIU Xu-dong, CAO Hui, TU Lin

Tumor. 2023, 43(08): 662-671. https://doi.org/10.3781/j.issn.1000-7431.2023.2210-0751

Abstract (389) Download PDF (1033)

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ETS variant gene 1 (ETV1) is an oncogene that plays an important role in embryonic development and malignant progression of tumors. Chromosomal translocations, gene amplifications, and activation of the mitogen activated protein kinase (MAPK) signal pathways lead to the up-regulation of ETV1, and then ETV1, as a transcription factor, regulates the expression of downstream target genes by binding to their promoters or enhancers, thereby playing a pivotal role in the occurrence and development of prostate cancer, gastrointestinal stromal tumor (GIST) and breast cancer. ETV1 is also a potential tumor biomarker, which has clinical value in diagnosis and prognostic evaluation in various tumors, and strategies targeting ETV1 can provide new treatment options to tumor patients. This article discusses the mechanisms of ETV1 activation and pro-oncogenic mechanisms driven by ETV1, and summarizes and prospects the clinical application of ETV1 as a tumor biomarker and therapeutic target.

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Review

Progress in immune checkpoint inhibitor therapy in advanced hepatocellular carcinoma

LI Xin , GAO Jian , TU Hong

Tumor. 2021, 41(12): 866-875. https://doi.org/10.3781/j.issn.1000-7431.2021.2109-0666

Abstract (151) Download PDF (1016)

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Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, and most cases are diagnosed at advanced stage. The multikinase inhibitors sorafenib and lenvatinib are currently first-line therapies for advanced HCC, but the response rates are limited and the drug resistances are increasing. In recent years, the immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies, have demonstrated promising efficacy in cancer clinical trials. Up to now, ICIs such as nivolumab, pembrolizumab and carrelizumab have been approved for the therapy of advanced HCC. Furthermore, the ICIs combination treatments, including ICIs combined with vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors, other ICIs, or topical remedy, are being tested in clinical trials. In particular, the combination therapy of atezolizumab and bevacizumab is significantly superior to sorafenib in prolonging the overall survival, so it is granted as the first-line therapy for advanced HCC. This paper reviews the underlying mechanism of ICIs therapy for advanced HCC and the results of clinical trials and discuss the drawbacks and the potential of ICIs.

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Original Research

BRCA1/2 mutation status affects the choice of operative approach in breast cancer patients

FU Fenfen , SUN Jie , ZHANG Dongjie , CHU Futao , ZHANG Chun , ZHANG Guofeng , XIE Yuntao

Tumor. 2022, 42(03): 165-171. https://doi.org/10.3781/j.issn.1000-7431.2021.2109-0686

Abstract (232) Download PDF (1007)

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Objective: To investigate the effect of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations on the choice of operative approach for breast cancer patients.

Methods: A total of 130 patients with primary breast cancer who underwent genetic testing for BRCA1/2 germline mutation and the surgical operation were treated in Department of Breast Surgery, Peking University International Hospital from December 2017 to June 2021. The clinical and pathological information of the patients were collected, including age of disease onset, family history of breast cancer and/or ovarian cancer, unilateral or bilateral breast cancer, pathological type, histologic grade, tumor size, immunohistochemistry, axillary lymph node metastasis before treatment, neoadjuvant chemotherapy and operative approach. The rates of different operative approaches were compared between BRCA1/2 and non-BRCA1/2 mutation carriers.

Results: Among 130 patients, 23 (17.7%) patients carried BRCA1/2 germline mutation. The operative approaches were significantly different between BRCA1/2 and non-BRCA1/2 mutation carriers (P < 0.01). As compared with the non-BRCA1/2 mutation carriers, the rate of breast-conserving surgery in 23 patients carrying BRCA1/2 mutation was lower with statistical significance (21.7% vs 50.5%), and the rate of unilateral mastectomy without contralateral prophylactic mastectomy was also lower with statistical significance (30.4% vs 49.5%), but the rate of unilateral mastectomy plus contralateral prophylactic mastectomy was higher with statistical significance (47.8% vs 0.0%).

Conclusion: BRCA1/2 mutation status can significantly influence the surgical decision for breast cancer patients. BRCA1/2 mutation carriers prefer to unilateral mastectomy or unilateral mastectomy plus contralateral prophylactic mastectomy rather than breast-conserving surgery.

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Review

Progress in CDK12 mutation in occurrence and development of prostate cancer and its clinical diagnosis and treatment

DU Xinxing, XIA Binbin, WU Fan, DONG Baijun, XUE Wei

Tumor. 2022, 42(03): 213-220. https://doi.org/10.3781/j.issn.1000-7431.2022.2104-0222

Abstract (407) Download PDF (1004)

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The high heterogeneity of molecular biology and gene level of prostate cancer leads to different treatment reactions and clinical outcomes. With the development of genomics and sequencing technology, people have a deeper understanding of the genomic characteristics of prostate cancer. CDK 12 mutation has been reported to be closely related to the adverse clinical outcome of prostate cancer, and may become a potential therapeutic marker for different treatment schemes. This review summarizes the data and research status of CDK12 mutation in prostate cancer, discusses the molecular and clinical characteristics of prostate cancer carrying CDK12 mutation and the response to different treatment schemes, and expounds the significance of CDK12 mutation in the occurrence and development of prostate cancer and its clinical diagnosis and treatment.

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Review

The progress of immune checkpoint inhibitors in soft tissue sarcoma

WU Hanxiao, CHEN Rui, FENG Xiang

Tumor. 2021, 41(02): 139-148. https://doi.org/10.3781/j.issn.1000-7431.2021.55.442

Abstract (159) Download PDF (929)

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Soft tissue sarcomas (STS) are mesenchymal malignant tumors with variable biological behaviors. The current main treatments for STS involve surgery with or without neoadjuvant or adjuvant chemotherapy /radiotherapy. The immune checkpoints refer to inhibitory pathways in the immune system. The dysfunction of the immune checkpoints is one of the main mechanism by which tumors evade the immune system. There are lots of clinical trials based on immune checkpoint inhibitors to treat malignancy with promising efficacy. This review summarizes the ongoing or completed clinical trials of immune checkpoint inhibitors in STS. We focus on the treatment strategies combine immune checkpoint inhibitors with neoadjuvant radiation therapies. Besides, the present review discusses whether it is possible for the treatment strategies which combine immune checkpoint inhibitors with targeted therapies or chemotherapies to become established therapies in the future.

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Review

Progress in research on myeloma bone disease

LIU Xujian, ZHANG Xia, ZHANG Qianqian, FENG Helin

Tumor. 2020, 40(01): 76-80. https://doi.org/10.3781/j.issn.1000-7431.2020.55.522

Abstract (168) Download PDF (918)

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Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). The pathogenesis of MBD is associated with the increase of osteoclast activity and the inhibition of osteoblast function, which seriously affects the quality of life of patients. Normal bone remodeling is maintained by bone cells, osteoclasts and osteoblasts balancing bone formation and bone resorption. A variety of cytokines can affect bone formation and bone resorption by regulating the activity of bone cells, osteoclasts and osteoblasts. Recent studies have reported that the molecules and pathways related to osteoclast activation and osteoblastic inhibition include the receptor activator of nuclear factor-κB ligand/osteoprotegerin pathway, activin-A, Wnt signal inhibitor Dickkopf-1 (DKK1) and sclerostin, etc. These molecules can affect tumor growth and provide the possibility for the development of new drugs and the treatment of MBD and MM. This article reviews the latest progress in the pathogenesis and treatment of MBD.

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