pak5-promotes-esophageal-squamous-cell-carcinoma-progression-revealed

PAK5 Promotes Esophageal Squamous Cell Carcinoma Progression Revealed by Transcriptomic Profiling

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related mortality globally, particularly in Asia. Due to the lack of early ...

The Second Affiliated Hospital of Hainan Medical University

Small cell lung cancer (SCLC), an aggressive and devastating malignancy, is characterized by rapid growth and early metastasis. Although most patients respond to first-line chemotherapy, the majority of patients rapidly relapse and have a relatively poor prognosis. Fortunately, immunotherapy, mainly including antibodies that target the cytotoxic T lymphocyte antigen-4 (CTLA-4), checkpoints programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) to block immune regulatory checkpoints on tumor cells, immune cells, fibroblasts cells and endothelial cells, has achieved the milestone in several solid tumors, such as melanoma and non-small-cell lung carcinomas (NSCLC). In recent years, immunotherapy has made progress in the treatment of patients with SCLC, while its response rate is relatively low to monotherapy. Interestingly, the combination of immunotherapy with other therapy, such as chemotherapy, radiotherapy, and targeted therapy, preliminarily achieve greater therapeutic effects for treating SCLC. Combining different immunotherapy drugs may act synergistically because of the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of chemoradiotherapy in immunotherapy may augment antitumor immune responses because chemoradiotherapy can enhance tumor cell immunogenicity by rapidly inducing tumor lysis and releasing tumor antigens. In addition, since immunotherapy drugs and the molecular targets drugs act on different targets and cells, the combination of these drugs may achieve greater therapeutic effects in the treatment of SCLC. In this review, we focused on the completed and ongoing trials of the combination therapy for immunotherapy of SCLC to find out the rational combination strategies which may improve the outcomes for SCLC.

Combination therapy: Future directions of immunotherapy in small cell lung cancer.

Lung cancer has attracted much attention because of its high morbidity and mortality worldwide. The advent of immunotherapy approaches, especially the application of immune checkpoint inhibitors (ICIs) has dramatically changed the treatment of lung cancer, but a novel and unexpected pattern of treatment response-- pseudoprogression, has been observed simultaneously which complicates the routine clinical evaluation and management. However, manifestations of pseudoprogression vary and there are many disputes on immune-related response assessment and corresponding treatments for lung cancer. Therefore, we summarized the possible mechanisms, clinical manifestations and corresponding treatment measures of pseudoprogression in lung cancer, as well as potential methods to differentiate pseudoprogression from true tumor progression.

Pseudoprogression in lung cancer patients treated with immunotherapy.

Small-cell lung cancer (SCLC) is a highly proliferative, invasive lung cancer with poor prognosis. Chemotherapy is still the standard first-line treatment for SCLC, but many patients relapse due to chemoresistance. Along with advances in immunology, it is essential to investigate potential indicators of the immune response and the prognosis of SCLC. Using bioinformatics analysis, we identified 313 differentially expressed genes (DEGs) in SCLC and normal lung samples, and we found that four upregulated genes (, , , and ) were associated with platinum resistance, while immune-related genes (HLA family genes) were downregulated in SCLC. Then, a prognostic prediction model was constructed for SCLC based on those genes. Immune cell infiltration analysis showed that antigen presentation was weak in SCLC, and  expression was negatively correlated with CD8+ T cells, while  expression was positively correlated with M1 macrophages, memory B cells, and CD8+ T cells. We also found that  was related to poor prognosis and inversely correlated with , which was verified with immunohistochemical staining in 151 SCLC specimens. Our study findings indicated that  may be a potential prognosis indicator and a target to reverse the immunosuppressive tumor microenvironment of SCLC.

Chemotherapy- and Immune-Related Gene Panel in Prognosis Prediction and Immune Microenvironment of SCLC.

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan-Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3-5) to 11 months (95% CI 8-12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38-50) and 25% (95 CI 20-30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19-29) and 6% (95 CI 3-9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88-2.72, p value < 0.001) was an adverse independent prognostic factor for patients. This study concludes that CDS prolonged survival in patients with gastric cancer with liver metastases. Due to the lack of information on the quality of life, biomarkers, targeted therapies, and immunotherapy in the SEER database, the observed improved survival rates following CDS of hepatic metastasis from gastric cancer requires prospective studies that take these factors into account to properly address the survival advantages and impact on quality of life of such a method.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer.

Esophageal ulcers can arise not only from malignant lesions but also from benign diseases, such as tuberculosis. These ulcers may mimic the radiological features of esophageal malignancy or tuberculosis on PET/CT, leading to diagnostic challenges.

Unusual presentation of esophageal tuberculosis: a case study.

Comment on The Study of NRG258: Limitations and Future Directions.

Radioresistance is a common cause of poor radiation therapy effectiveness for non-small cell lung cancer. Finding molecular targets or methods to enhance radiosensitivity or overcome radioresistance is crucial. This study aimed to investigate the effects of MDMX on modulating radiosensitivity in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).

MDMX enhances radiosensitivity in lung adenocarcinoma and squamous cell carcinoma by inhibiting P53-mediated autophagy.

This study was conducted to assess the efficacy and safety of magnetic resonance (MR)-guided hypofractionated radiotherapy in patients with unresectable hepatocellular carcinoma (HCC). Machine learning-based radiomics was utilized to predict responses in these patients.

Machine Learning Radiomics for Predicting Response to MR-Guided Radiotherapy in Unresectable Hepatocellular Carcinoma: A Multicenter Cohort Study.

With the programmed cell death protein 1 (PD-1) blockade toripalimab, omitting highly toxic concurrent cisplatin may be feasible for nasopharyngeal carcinoma (NPC) without compromising survival.

Article	Year
Combination therapy: Future directions of immunotherapy in small cell lung cancer. Translational oncology\| PubMed ID: 33065386	2021
Pseudoprogression in lung cancer patients treated with immunotherapy. Critical reviews in oncology/hematology\| PubMed ID: 34800651	2022
Chemotherapy- and Immune-Related Gene Panel in Prognosis Prediction and Immune Microenvironment of SCLC. Frontiers in cell and developmental biology\| PubMed ID: 35784467	2022
Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico\| PubMed ID: 37606846	2024
Unusual presentation of esophageal tuberculosis: a case study. BMC infectious diseases\| PubMed ID: 39748310	2025
Comment on The Study of NRG258: Limitations and Future Directions. Journal of clinical oncology : official journal of the American Society of Clinical Oncology\| PubMed ID: 40209127	2025
MDMX enhances radiosensitivity in lung adenocarcinoma and squamous cell carcinoma by inhibiting P53-mediated autophagy. Cellular oncology (Dordrecht, Netherlands)\| PubMed ID: 40327296	2025
Machine Learning Radiomics for Predicting Response to MR-Guided Radiotherapy in Unresectable Hepatocellular Carcinoma: A Multicenter Cohort Study. Journal of hepatocellular carcinoma\| PubMed ID: 40370640	2025
Toripalimab Combination Therapy Without Concurrent Cisplatin for Nasopharyngeal Carcinoma: The DIAMOND Randomized Clinical Trial. JAMA\| PubMed ID: 40839372	2025
Comments on the Study of Outcomes After Radiation for Oligoprogressive Disease Sites in Patients With -Mutant Lung Cancer. JCO precision oncology\| PubMed ID: 40929618	2025

Yuecan Zeng

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