Cancer pathogenesis and therapy最新文献

{"title":"Dostarlimab in the treatment of mismatch repair deficient recurrent or advanced endometrial cancer","authors":"Siddhant Shukla ,&nbsp;Harsh Patel ,&nbsp;Shuzhen Chen ,&nbsp;Rainie Sun ,&nbsp;Liuya Wei ,&nbsp;Zhe-Sheng Chen","doi":"10.1016/j.cpt.2023.10.003","DOIUrl":"10.1016/j.cpt.2023.10.003","url":null,"abstract":"<div><p>Dostarlimab, a programmed death receptor-1 (PD-1)-blocking IgG4 humanized monoclonal antibody, gained accelerated approval from the US Food and Drug Administration (FDA) in April 2021, and received a full approval in February 2023. Dostarlimab was approved for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC) that progressed during or after prior treatment who have no other suitable treatment options. Herein, we review the structure-based mechanism of action of dostarlimab and the results of a clinical study (GARNET; NCT02715284) to comprehensively clarify the efficacy and toxicity of the drug. The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized, multicenter, open-label, multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy. Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses. Then, patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity. The overall response rate, as determined by shrinkage in tumor size, was 41.6% (95% confidence interval [CI]; 34.9, 48.6), with 34.7 months as the median response duration. In conclusion, dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC. However, its efficacy in other cancer subtypes, the development of resistance to monotherapy, and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 3","pages":"Pages 135-141"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294971322300085X/pdfft?md5=da6c271bd6c1eecc55a01fce646df3ba&pid=1-s2.0-S294971322300085X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135852344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overlap in oncogenic and pro-inflammatory pathways associated with areca nut and nicotine exposure","authors":"Krati Garg ,&nbsp;Anuj Kumar ,&nbsp;Vidisha Kizhakkethil ,&nbsp;Pramod Kumar ,&nbsp;Shalini Singh","doi":"10.1016/j.cpt.2023.09.003","DOIUrl":"10.1016/j.cpt.2023.09.003","url":null,"abstract":"<div><h3>Background</h3><p>Betel nut/areca nut/<em>Areca catechu</em> is one of the most commonly used psychoactive substance, and is also a major preventable cause of cancer. Unlike other psychoactive substances, such as nicotine, the mechanisms underlying addiction to areca nuts and related oncogenesis remain elusive. Recent reports suggest a possible overlap in the mechanisms of action of nicotine and areca nuts in the human body. Thus, this study aimed to investigate the interactome of human proteins associated with areca nut exposure and the intricate similarities and differences in the effects of the two psychoactive substances on humans.</p></div><div><h3>Methods</h3><p>A list of proteins associated with areca nut use was obtained from the available literature using terms from Medical Subject Headings (MeSH). Protein-protein interaction (PPI) networks and functional enrichment were analyzed. The results obtained for both psychoactive substances were compared.</p></div><div><h3>Results</h3><p>Given the limited number of common proteins (36/226, 16%) in the two sets, a substantial overlap (612/1176 nodes, 52%) was observed in the PPI networks, as well as in Gene Ontology. Areca nuts mainly affect signaling pathways through three hub proteins (alpha serine/threonine-protein kinase, tumor protein 53, and interleukin-6), which are common to both psychoactive substances, as well as two unique hub proteins (epidermal growth factor receptor and master regulator of cell cycle entry and proliferative metabolism). Areca nut-related proteins are associated with unique pathways, such as extracellular matrix organization, lipid storage, and metabolism, which are not found in nicotine-associated proteins.</p></div><div><h3>Conclusions</h3><p>Areca nuts affect regulatory mechanisms, leading to systemic toxicity and oncogenesis. Areca nuts also affect unique pathways that can be studied as potential markers of exposure, as well as targets for anticancer therapeutic agents.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 3","pages":"Pages 187-194"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000538/pdfft?md5=b53504edae65d6c0b6c5194a5a7c7804&pid=1-s2.0-S2949713223000538-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135348578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between visceral obesity and prognosis in patients with stage IVB cervical cancer receiving radiotherapy and chemotherapy","authors":"Chao Ji,&nbsp;Silin Liu,&nbsp;Che Wang,&nbsp;Jie Chen,&nbsp;Jin Wang,&nbsp;Xinyue Zhang,&nbsp;Jinlu Ma,&nbsp;Mengjiao Cai","doi":"10.1016/j.cpt.2023.09.002","DOIUrl":"10.1016/j.cpt.2023.09.002","url":null,"abstract":"<div><h3>Background</h3><p>Concurrent chemoradiotherapy is the preferred treatment for stage IVB cervical cancer; however, some patients experience a poor prognosis. The prognostic significance of body composition indicators, including visceral obesity, has been extensively investigated in patients with cancer. This study aimed to assess the impact of body composition indicators, specifically pretreatment fat content, on the survival outcomes of patients with stage IVB cervical cancer.</p></div><div><h3>Methods</h3><p>We retrospectively analyzed clinical information from patients diagnosed with stage IVB cervical cancer between 2010 and 2018. We measured visceral obesity (visceral-to-subcutaneous adipose tissue area ratio [VSR]) and skeletal muscle index (SMI) on pretreatment computed tomography (CT) images. We evaluated the impact of these body composition parameters on the prognosis of patients with cervical cancer.</p></div><div><h3>Results</h3><p>Overall, 116 patients were included, 81 of whom had complete clinical and imaging information. Based on the cut-off values from X-tile analysis, we categorized patients into high and low VSR and SMI groups. The overall survival (OS) rate of patients with a high VSR was significantly higher than that of patients with a low VSR (<em>P</em> = 0.022). Multivariate Cox regression analysis showed that a low VSR was an independent risk factor for the prognosis of patients with stage IVB cervical cancer.</p></div><div><h3>Conclusion</h3><p>Visceral obesity before radiotherapy and chemotherapy has a protective effect on the prognosis of patients with stage IVB cervical cancer, while low muscle index and VSR are associated with poor prognosis.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 3","pages":"Pages 180-186"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000526/pdfft?md5=06cf2a97d07151a9047f6bd66510398a&pid=1-s2.0-S2949713223000526-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135387622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing post-treatment outcomes in patients with oral cancer: Integrating interventions and psychosocial support","authors":"Ponnambalam Ragini Yaashikaa","doi":"10.1016/j.cpt.2024.06.005","DOIUrl":"10.1016/j.cpt.2024.06.005","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 318-320"},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713224000466/pdfft?md5=7427177f4f8429c29640eb8efb78b26e&pid=1-s2.0-S2949713224000466-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into digestive tract tumors","authors":"Zhidong Gao,&nbsp;Zhanlong Shen,&nbsp;Shuo Wang,&nbsp;Yingjiang Ye","doi":"10.1016/j.cpt.2024.06.002","DOIUrl":"10.1016/j.cpt.2024.06.002","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 217-218"},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713224000430/pdfft?md5=644cd2522c4a9c8bfad1b2b01e167769&pid=1-s2.0-S2949713224000430-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence rate and risk factors of second primary neoplasms among older patients with hematological malignancies: Insights from a Chinese single-center experience (1997–2021)","authors":"","doi":"10.1016/j.cpt.2024.06.001","DOIUrl":"10.1016/j.cpt.2024.06.001","url":null,"abstract":"<div><h3>Background</h3><div>Patients with hematological malignancies face an increased risk of developing second primary neoplasms due to various factors, including immune system compromise and chemotherapy-related effects. However, the incidence and associated risk factors in older patients remain poorly understood. This study aimed to assess the incidence, identify risk factors, and evaluate their impact on survival outcomes among older patients with hematological malignancies.</div></div><div><h3>Methods</h3><div>This retrospective single-center study analyzed data from 163 patients, focusing on the occurrence of second primary neoplasms. Cumulative incidence rates were calculated, and risk factor analysis was conducted using a competing risk model.</div></div><div><h3>Results</h3><div>Among 124 eligible patients with a total follow-up duration of 572.57 person-years, the incidence rate of second primary neoplasms was 15.72/1000 person-years. The standardized incidence ratio (SIR) was 0.81 (95% confidence interval [CI] [0.39–1.48], <em>P</em> = 0.518). History of radiotherapy emerged as a significant risk factor (sub-distribution hazard ratio [SHR] = 21.61 [2.81–166.14], <em>P</em> = 0.003), whereas regular natural killer (NK) cell infusion was associated with reduced risk (SHR = 3.25 e−8 [9.81 e−9–1.08 e−7], <em>P</em> ＜ 0.001).</div></div><div><h3>Conclusions</h3><div>These findings underscore the importance of informing older patients with hematological malignancies about the long-term risks of second primary neoplasms. Healthcare providers should carefully weigh risk factors when formulating treatment strategies. The results are valuable for investigating the fundamental principles underlying the occurrence and progression of second primary neoplasms.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 285-291"},"PeriodicalIF":0.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713224000429/pdfft?md5=69423fabed1335c73e775c2c4dee5c20&pid=1-s2.0-S2949713224000429-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141415759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between autoimmunity-related disorders and prostate cancer: A Mendelian randomization study","authors":"","doi":"10.1016/j.cpt.2024.03.002","DOIUrl":"10.1016/j.cpt.2024.03.002","url":null,"abstract":"<div><h3>Background</h3><div>Although many epidemiological studies and meta-analyses have reported an association between autoimmune disorders and prostate cancer, none has reported a clear correlation or the direction of the association. The purpose of our study was to explore the potential relationship between autoimmunity-related disorders and prostate cancer using Mendelian randomization (MR).</div></div><div><h3>Methods</h3><div>We retrieved literature from PubMed using the keywords “autoimmune disorder” AND “prostate cancer” to find more clues on the correlation between prostate cancer and autoimmunity-related disorder. Based on this literature search, we selected 16 autoimmunity-related disorders that had genome-wide association study (GWAS) data and may be associated with prostate cancer. The inverse variance weighting (IVW) method was applied as our primary analysis for two-sample MR and multivariate MR analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). We further verified the robustness of our conclusions using a series of sensitivity analyses.</div></div><div><h3>Results</h3><div>The autoimmunity-related diseases selected include rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthropathies, and polymyalgia rheumatica. The results of inverse variance weighting (IVW suggested that six diseases were associated with the development of prostate cancer. The three diseases that may increase the risk of prostate cancer are rheumatoid arthritis (<em>P</em> = 0.001), coxarthrosis (<em>P</em> &lt; 0.001), and gonarthrosis (<em>P</em> = 0.008). The three possible protective factors against prostate cancer are primary sclerosing cholangitis (<em>P</em> = 0.001), autoimmune hyperthyroidism (<em>P</em> = 0.011), and psoriatic arthropathies (<em>P</em> = 0.001). Horizontal pleiotropy was not observed in the MR-Egger test.</div></div><div><h3>Conclusions</h3><div>Our findings provide predictive genetic evidence for an association between autoimmune disorders and prostate cancer. Further research is needed to explore the underlying mechanisms of comorbidities at the molecular level.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 292-298"},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713224000211/pdfft?md5=aadc6f8c5ef4020d01d627f2bf5d8edb&pid=1-s2.0-S2949713224000211-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140402676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"","doi":"10.1016/S2949-7132(24)00006-5","DOIUrl":"https://doi.org/10.1016/S2949-7132(24)00006-5","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 2","pages":"Page OFC"},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713224000065/pdfft?md5=26af0302537c524214c7a7fa8f3926c0&pid=1-s2.0-S2949713224000065-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140297064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term adoptive immunotherapy achieves complete response and bone lesion repair in an elderly patient with macrofocal multiple myeloma","authors":"","doi":"10.1016/j.cpt.2024.03.001","DOIUrl":"10.1016/j.cpt.2024.03.001","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 314-317"},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713224000193/pdfft?md5=c4298a9c33216dd6f07df87781c1ec58&pid=1-s2.0-S2949713224000193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140275004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of anlotinib plus penpulimab as second-line treatment for small cell lung cancer: A multicenter, open-label, single-arm phase II trial","authors":"","doi":"10.1016/j.cpt.2024.02.001","DOIUrl":"10.1016/j.cpt.2024.02.001","url":null,"abstract":"<div><h3>Background</h3><div>Currently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy.</div></div><div><h3>Methods</h3><div>This study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg <em>quaque die</em> [QD], days 1–14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1–14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR).</div></div><div><h3>Results</h3><div>From April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7–66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9–11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6–not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21).</div></div><div><h3>Conclusions</h3><div>In patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation.</div></div><div><h3>Trial registration</h3><div>No. <span><span>NCT04203719</span><svg><path></path></svg></span>, <span><span>https://clinicaltrials.gov/</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 268-275"},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713224000041/pdfft?md5=00ec1c474c71cd0b292b4f28a4c4d00e&pid=1-s2.0-S2949713224000041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139883467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}