Objective: To design protein binders of human epidermal growth factor receptor 2 (HER2, also known as ErbB2) using de novo protein design and to preliminarily evaluate their biological effects on tumor cells.

Methods: Based on de novo protein design strategy, utilizing RosettaDesign and ProteinMPNN algorithms to design the binding proteins targeting ErbB2. Concurrently, AlphaFold was applied to assess structural accuracy of the protein binders and their interactions with ErbB2. Subsequently, yeast surface display (YSD) technology combined with dual-fluorescence high-throughput flow cytometry were performed to screen for protein binders capable of specifically binding ErbB2. Selected binding proteins were expressed and purified in E. coli system. Bio-layer interferometry (BLI) was used to validate the specific binding capability of the purified protein binders to ErbB2. Finally, Western blotting and CCK-8 assays were used to evaluate the effects of the candidate binding proteins on downstream signaling of ErbB2 and cell proliferation capacity in ovarian cancer (SK-OV-3) and pancreatic cancer (BxPC-3) cell lines, respectively.

Results: In This study, the design of protein binders targeting ErbB2 was successfully designed. A corresponding binding protein library was established, and a protein binder that specifically binds to ErbB2 was screened out from it. After BLI verification, this protein binder could effectively bind to ErbB2. Further investigation revealed that this protein binder could effectively inhibited cell proliferation and reduced the phosphorylation level of AKT from ErbB2 downstream signaling pathway in ErbB2-high-expressing SK-OV-3 and BxPC-3 cells.

Conclusion: Based on the strategy of de novo protein design, this study successfully constructed a protein binder that can effectively bind to ErbB2, and this binder can effectively inhibit the activation of the downstream signaling pathway mediated by ErbB2 and the proliferation of tumor cells. This indicates the potential application value of de novo designed protein binders targeting ErbB2 in cancer therapy, and provides a novel research approach for the field of targeted tumor therapy.

Objective: To investigate the role of endoplasmic reticulum stress (ERS)-related long noncoding RNA (lnc RNA)-Gm9795 in the progression of hepatocellular carcinoma (HCC).

Methods: This retrospective cohort study included 80 HCC patients who underwent routine surgical procedures at our hospital from 2014 to 2020. Collect clinical data from all patients and use real-time fluorescence quantitative PCR to detect the expression level of Gm9795 in 80 patients' cancer and adjacent tissues, as well as in HCC cells (HepG2, Hep3B, HCCLM3, and Huh7). Analyze the correlation between Gm9795 expression and overall survival time and recurrence free survival time of HCC patients. Constructing HCCLM3 cells overexpressing Gm9795 through lentiviral infection, and constructing Huh7 cells silencing Gm9795 expression through liposome transfection. The proliferation ability of cells was evaluated using CCK-8 method and cell clone formation assay, while the migration and invasion ability of cells were detected using Transwell chamber assay. Identification of Gm9795 specific binding protein by mass spectrometry (MS). The effect of overexpressing or silencing Gm9795 expression on the expression of C/EBP homologous protein (CHOP) gene was detected by Western blotting. The CHOP gene was simultaneously transferred into HCCLM3 cells overexpressing Gm9795, and the effects of up-regulating CHOP expression level on the proliferation, migration, and invasion ability of HCCLM3 cells were evaluated using CCK-8 method, cell clone formation assay, and Transwell chamber assay.

Results: Compared with the corresponding non tumor tissues, the expression level of Gm9795 was significantly up-regulated in HCC tissues (P<0.001). All HCC cells exhibited significantly higher levels of Gm9795 expression than LO2 cells (all P<0.05). Higher expression levels of Gm9795 are associated with invasive clinical pathological features, including tumor size, multiple tumors, Barcelona Clinic Liver Cancer (BCLC) staging, and portal vein thrombosis (all P<0.05). The results of multivariate analysis showed that Gm9795 expression was an independent risk factor for overall survival and recurrence free survival in HCC patients (both P<0.05). The higher expression of Gm9795 was significantly correlated with shorter overall survival and recurrence free survival in the cohort (both P<0.01). Compared with the Vector group, the Gm9795 group showed a significant increase in cell viability, clone number, migration, and invasion of HCCLM3 cells (all P<0.01); Compared with the siNC group, the cell viability, clone number, migration, and invasion of Huh7 cells were significantly reduced in the siGm9795-1 and siGm9795-2 groups (all P<0.01). CHOP was identified as a Gm9795 specific binding protein by MS. Compared with the Gm9795+Vector group, the CHOP+Gm9795 group showed significant reductions in cell viability, clone number, migration, and invasive cell numbers (all P<0.01).

Conclusions: Gm9795 is up-regulated in HCC tissues, and the high expression of Gm9795 is an independent risk factor for the overall survival of HCC patients. Gm9795 promotes the proliferation and invasion of HCC cells, and its mechanism may be related to the inhibition of ERS mediated by CHOP signaling pathway.

Objective: To explore the diagnosis and treatment strategies of multiple primary malignancies (MPM).

Methods: The medical records and the process of diagnosis and treatment of a patient with heterochronous double primary cancer were retrospectively analyzed, and the treatment strategy was discussed by multi-disciplinary team (MDT).

Results: A female patient with heterochronous double primary cancer was reported. The first primary tumor was gastric cancer and the second primary tumor was lung cancer. The first primary tumor was diagnosed at 67 years of age, and the interval between the first and second primary tumors was 13 months. Pleural metastasis and pelvic metastasis occurred during the follow-up. Pleural metastasis originated from lung cancer, and pelvic metastasis was considered as gastric cancer implantation. Tumor MDT discussion was conducted at each stage of diagnosis and treatment, and the histopathological diagnosis was confirmed by puncture biopsy or surgical resection. The patient received systemic therapy combined with local treatment for metastases of different tumors and had a longer overall survival (67 months). Side effects were tolerable, and the quality of life was satisfactory throughout the treatment period.

Conclusion: For patients with MPM, it is necessary to actively carry out MDT discussion, clarify the histopathological diagnosis, evaluate the clinicopathological and metastatic characteristics, and implement active and effective treatment.

Gastric cancer is one of the malignant tumors with strong invasion and heterogeneity. Individualized treatment of gastric cancer based on precise classification guidance is currently a research hotspot. Microsatellite instability-high (MSI-H) gastric cancer has specific clinical features, tumor microenvironment, and pathological characteristics, which have been used as tumor markers to evaluate the prognosis of gastric cancer patients. In recent years, immunotherapy has brought new hope for the treatment of gastric cancer patients, among whom MSI-H patients are considered the advantageous population for immunotherapy. This paper reports a case of MSI-H metastatic gastric cancer receiving immunotherapy combined with chemotherapy, and provides reference for clinical practice based on literature review.

Liver cancer stands as one of the most lethal malignant tumors globally, and liver transplantation presents a potent and effective therapeutic approach for affected individuals. However, the post-transplantation immune regulation is critical for the survival of the graft and the long-term prognosis of the patient. Energy metabolism plays a pivotal role in both the tumor microenvironment and immunomodulation following liver transplantation. This review explores the metabolic mechanisms within the tumor microenvironment, energy metabolism characteristics in liver transplantation, and the impact of post-transplantation energy metabolism on reducing liver cancer recurrence and mitigating transplant rejection. By gaining an in-depth comprehension of the intricate interplay between metabolic pathways and immune regulation, it is envisioned that innovative therapeutic strategies can be formulated. These strategies aim to enhance the outcomes for liver transplant recipients and offer more efficacious treatment options for those afflicted with liver cancer.

Porphyrin and its derivatives exhibit diverse biochemical properties because of their unique molecular structures, and have been widely used and recognized in the field of tumor therapy. The applications of chemical modifications and nanotechnology have not only significantly enhanced the biological activity of porphyrins and their derivatives but also substantially improved the drug delivery efficiency. In addition, the applications of porphyrins and their derivatives in multiple therapeutic methods, including photodynamic therapy (PDT), sonodynamic therapy (SDT), radiotherapy and immunotherapy, have opened the door for the implementation of tumor multimodal treatment strategies. This cross-disciplinary integration facilitates the overcoming of limitations inherent to single-modality treatments, thereby synergistically enhancing overall therapeutic efficacy aganist tumors. This review systematically summarizes recent advances in the applications of porphyrins and their derivatives within the aforementioned therapeutic treatments, and the challenges and future development potential of porphyrins and their derivatives in tumor therapy are respectively discussed and prospected.

With the progression of global population aging, the incidence and mortality of prostate cancer (PCa) have been increasing year by year, drawing widespread attention from all sectors of society. Based on the synthetic lethality strategy, the U.S. Food and Drug Administration (FDA) has successively approved multiple poly ADP-ribose polymerase (PARP) inhibitors for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years. This advancement has greatly stimulated the interest of researchers in novel synthetic lethal combination: the ataxia telangiectasia-mutated (ATM) gene and the ataxia telangiectasia and Rad3-related protein (ATR). In the DNA damage repair pathway, the ATM kinase primarily participates in the repair of DNA double-strand breaks, while ATR plays a crucial role in the repair of DNA single-strand breaks and exerts a positive regulatory function. ATR inhibitors are considered one of the most promising synthetic lethal targeted agents following PARP inhibitors, offering potential as a novel therapeutic option for patients with ATM gene mutations. However, current clinical research data on ATR inhibitors in the treatment of prostate cancer remain insufficient. Therefore, a deeper understanding of the synthetic lethality mechanism involving the ATM/ATR kinase combination is of crucial importance for advancing precision therapy of prostate cancer.

Osteosarcoma is the most common primary malignant bone tumor, typically treated with a combination of surgery and chemotherapy in clinical practice. However, the increasing prevalence of chemotherapy resistance poses a significant challenge. Chemotherapy resistance can lead to a sharp decline in patients’ survival rates. Traditional Chinese medicine, known for its low cost, wide-ranging efficacy, and diverse varieties, has attracted significant attention from researchers. Their attempts to investigate the sensitizing effect of extracted ingredients on osteosarcoma chemoresistance both in vitro and in vivo have yielded promising results. This review has summarized the studies of single traditional Chinese medicine ingredients on reversing osteosarcoma chemoresistance by the mechanisms of chemoresistance, and found that the current research of the clinical mechanism of traditional Chinese medicine ingredients in reversing osteosarcoma chemoresistance is still lacking, indicating significant potential for future development. Utilizing the theory of herbal medicine properties as the theoretical basis for ingredient development may provide novel strategies for the development of new therapeutic approaches.

Among solid tumors, melanoma brain metastases (MBM) has the highest incidence and is the leading cause of death in patients with advanced melanoma. BRAF/MEK inhibitors and immune checkpoint inhibitors are currently effective methods for the treatment of brain metastases in melanoma patients. However, due to the existing blood-brain barrier and special intracranial microenviroment, the overall survival of patients has not been significantly improved, which has become a major difficulty in current treatment. Therefore, the study of brain metastases mechanism is of great significance for improving the treatment of advanced patients and improving the prognosis and survival rate of patients. In this paper, the research progress of MBM mechanism in recent years is summarized, in order to provide new ideas for follow-up clinical work.

Epidermal growth factor receptor (EGFR) gene exon 20 insertion mutation is a common driver gene activation mutation in non-small cell lung cancer (NSCLC). Tumors harboring this gene mutation are characterized by high heterogeneity, high malignancy, low detectability, poor response to conventional therapies, and poor prognosis. In recent years, significant progress has been made in the study of EGFR ex20ins mutation. The wide application of next-generation sequencing has improved the detection rate. The United States has approved the relevant indications of amivantamab in NSCLC patients with EGFR ex20ins mutation. A variety of new drugs have also achieved good results in previous studies. This article will summarize the structural characteristics, detection methods and clinical treatment progress of NSCLC patients with EGFR ex20ins mutations, hoping to provide help for the choice of clinical treatment for such patients.

At present, the treatment level of cancer has made great progress. However, cancer therapy-related cardiovascular toxicity can adversely affect the prognosis of cancer patients. Studies have found that the high risk of cardiovascular toxicity has gradually become an important factor for non-tumor mortality. Therefore, there is a growing interest in oncologic cardiology. However, there is still a lack of consensus on the optimal strategies for the identification, diagnosis, and intervention of cancer therapy-related cardiovascular toxicity. This article proposes for the first time the concept of “four early” measures for cardiovascular toxicity related to tumor treatment, namely early assessment of risk factors, early identification of clinical manifestations, early diagnosis through modern medical methods, and personalized intervention in the early stage after diagnosis. Combined with relevant research at home and abroad, this article also discusses the shortcomings of research on cardiovascular toxicity related to tumor treatment and proposes future development directions, aiming to provide reference for the prevention and treatment of cardiovascular toxicity events in patients undergoing anti-tumor treatment.