Ya-Xi Wu, Bing-Qian Li, Xiao-Qian Yu, Yu-Lin Liu, Rui-Hao Chui, Kai Sun, Dian-Guang Geng, Li-Ying Ma
Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.
{"title":"Histone deacetylase 6 as a novel promising target to treat cardiovascular disease","authors":"Ya-Xi Wu, Bing-Qian Li, Xiao-Qian Yu, Yu-Lin Liu, Rui-Hao Chui, Kai Sun, Dian-Guang Geng, Li-Ying Ma","doi":"10.1002/cai2.114","DOIUrl":"https://doi.org/10.1002/cai2.114","url":null,"abstract":"<p>Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.</p>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881007","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}
Disulfide, an essential compounds family, has diverse biological activity and can affect the dynamic balance between physiological and pathological states. A recently published study found that aberrant accumulation of disulfide had a lethal effect on cells. This mechanism of cell death, named disulfidptosis, differs from other known cell death mechanisms, including cuproptosis, apoptosis, necroptosis, and pyroptosis. The relationship between disulfidptosis and development of cancer, in particular endometrial carcinoma, remains unclear.
Methods
To address this knowledge gap, we performed a preliminary analysis of samples from The Cancer Genome Atlas database. The samples were divided equally into a training group and a test group. A total of 2308 differentially expressed genes were extracted, and 11 were used to construct a prognostic model.
Results
Based on the risk score calculated using the prognostic model, the samples were divided into a high-risk group and a low-risk group. Survival time, tumor mutation burden, and microsatellite instability scores differed significantly between the two groups. Furthermore, a between-group difference in treatment effect was predicted. Comparison with other models in the literature indicated that this prognostic model had better predictive anility.
Conclusion
The results of this study provide a general framework for understanding the relationship between disulfidptosis and endometrial cancer that could be used for clinical evaluation and selection of appropriate personalized treatment strategies.
{"title":"Identification of a disulfidptosis-related prognostic signature for prediction of the effect of treatment in patients with endometrial carcinoma","authors":"Lu Peng, Yuan Gao, Zifeng Cao, Yingxin Pang","doi":"10.1002/cai2.120","DOIUrl":"https://doi.org/10.1002/cai2.120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Disulfide, an essential compounds family, has diverse biological activity and can affect the dynamic balance between physiological and pathological states. A recently published study found that aberrant accumulation of disulfide had a lethal effect on cells. This mechanism of cell death, named disulfidptosis, differs from other known cell death mechanisms, including cuproptosis, apoptosis, necroptosis, and pyroptosis. The relationship between disulfidptosis and development of cancer, in particular endometrial carcinoma, remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To address this knowledge gap, we performed a preliminary analysis of samples from The Cancer Genome Atlas database. The samples were divided equally into a training group and a test group. A total of 2308 differentially expressed genes were extracted, and 11 were used to construct a prognostic model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Based on the risk score calculated using the prognostic model, the samples were divided into a high-risk group and a low-risk group. Survival time, tumor mutation burden, and microsatellite instability scores differed significantly between the two groups. Furthermore, a between-group difference in treatment effect was predicted. Comparison with other models in the literature indicated that this prognostic model had better predictive anility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results of this study provide a general framework for understanding the relationship between disulfidptosis and endometrial cancer that could be used for clinical evaluation and selection of appropriate personalized treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639631","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}
Jing Chen, Jing Yang, Yufang Liu, Xu Zhao, Juanjuan Zhao, Lin Tang, Mengmeng Guo, Ya Zhou, Chao Chen, Dongmei Li, Zhenke Wen, Guiyou Liang, Lin Xu
Background
Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer (NSCLC). The atypical mitogen-activated protein kinase 4 (MAPK4) has been shown to be involved in the pathogenesis of various diseases. However, the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear.
Methods
Adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group, respectively. The cell proliferation was analyzed with flow cytometry and immunofluorescence staining. The vascular density in tumor mass was analyzed by immunofluorescence staining. The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining, and so on.
Results
We found that the expression of MAPK4, which was dominantly expressed in local endothelial cells (ECs), was correlated with tumor angiogenesis of NSCLC. Furthermore, MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs (HUVECs). Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways, and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2 (ERK1/2) pathway but not Akt and c-Jun n-terminal kinase pathways. Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant, which was accompanied with increased transduction of the ERK1/2 pathway. Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC. Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo.
Conclusion
Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC. MAPK4 may thus represent a new target for NSCLC.
{"title":"MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer","authors":"Jing Chen, Jing Yang, Yufang Liu, Xu Zhao, Juanjuan Zhao, Lin Tang, Mengmeng Guo, Ya Zhou, Chao Chen, Dongmei Li, Zhenke Wen, Guiyou Liang, Lin Xu","doi":"10.1002/cai2.117","DOIUrl":"https://doi.org/10.1002/cai2.117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer (NSCLC). The atypical mitogen-activated protein kinase 4 (MAPK4) has been shown to be involved in the pathogenesis of various diseases. However, the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group, respectively. The cell proliferation was analyzed with flow cytometry and immunofluorescence staining. The vascular density in tumor mass was analyzed by immunofluorescence staining. The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining, and so on.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the expression of MAPK4, which was dominantly expressed in local endothelial cells (ECs), was correlated with tumor angiogenesis of NSCLC. Furthermore, MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs (HUVECs). Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways, and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2 (ERK1/2) pathway but not Akt and c-Jun n-terminal kinase pathways. Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant, which was accompanied with increased transduction of the ERK1/2 pathway. Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC. Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC. MAPK4 may thus represent a new target for NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556314","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}
Huiyi Liu, Lu Fu, Shuyu Jin, Xingdong Ye, Yanlin Chen, Sijia Pu, Yumei Xue
Background
With the emergence of cytotoxic T lymphocyte-associated protein-4 (CTLA-4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.
Methods
Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3–5 cardiac and vascular adverse events. These involved comparisons of CTLA-4 inhibitors to placebo, CTLA-4 inhibitors plus chemotherapy to chemotherapy alone, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone, and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method.
Results
Overall, 20 trials were included. CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00–1.75, p = 0.05). The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors (OR = 1.73, 95% CI: 1.13–2.65, p = 0.01), as well as the incidence rate of grades 3–5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08–3.70, p = 0.03). Compared with the non-CTLA-4 inhibitor group, CTLA-4 inhibitors plus chemotherapy, PD-1/PD-L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3–5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor, but the data were not statistically significant.
Conclusion
Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignanc
{"title":"Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients: A meta-analysis","authors":"Huiyi Liu, Lu Fu, Shuyu Jin, Xingdong Ye, Yanlin Chen, Sijia Pu, Yumei Xue","doi":"10.1002/cai2.116","DOIUrl":"https://doi.org/10.1002/cai2.116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With the emergence of cytotoxic T lymphocyte-associated protein-4 (CTLA-4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3–5 cardiac and vascular adverse events. These involved comparisons of CTLA-4 inhibitors to placebo, CTLA-4 inhibitors plus chemotherapy to chemotherapy alone, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone, and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 20 trials were included. CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00–1.75, <i>p</i> = 0.05). The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors (OR = 1.73, 95% CI: 1.13–2.65, <i>p</i> = 0.01), as well as the incidence rate of grades 3–5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08–3.70, <i>p</i> = 0.03). Compared with the non-CTLA-4 inhibitor group, CTLA-4 inhibitors plus chemotherapy, PD-1/PD-L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3–5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor, but the data were not statistically significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignanc","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556318","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}
Yulin Xu, Wei Shan, Qian Luo, Meng Zhang, Dawei Huo, Yijin Chen, Honghu Li, Yishan Ye, Xiaohong Yu, Yi Luo, He Huang
Background
Cancer-targeted T-cell receptor T (TCR-T) cells hold promise in treating cancers such as hematological malignancies and breast cancers. However, approaches to obtain cancer-reactive TCR-T cells have been unsuccessful.
Methods
Here, we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints. Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells, and then the expanded cells were applied to establish humanized mice. The human immune system was evaluated according to the kinetics of dendritic cells, monocytes, T-cell subsets, and cytokines. To fully stimulate the immune response and to obtain B-cell precursor NAML-6- and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells, we used the inactivated cells above to treat humanized mice twice a day every 7 days. Then, human T cells were processed for TCR β-chain (TRB) sequencing analysis. After the repertoires had been constructed, features such as the fraction, diversity, and immune signature were investigated.
Results
The results demonstrated an increase in diversity and clonality of T cells after treatment. The preferential usage and features of TRBV, TRBJ, and the V–J combination were also changed. The stress also induced highly clonal expansion. Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice.
Conclusions
We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools. Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells. It therefore has the potential to greatly benefit cancer treatment.
背景 癌症靶向 T 细胞受体 T（TCR-T）细胞有望治疗血液恶性肿瘤和乳腺癌等癌症。然而，获得癌症反应性 TCR-T 细胞的方法一直不成功。 方法 在这里，我们开发了一种新策略，利用具有特异性免疫指纹的特殊人源化小鼠模型筛选癌症靶向 TCR-T 细胞。通过对稳态外周血单核细胞进行三维培养，扩增稀有的稳态循环造血干细胞和祖细胞，然后将扩增的细胞用于建立人源化小鼠。根据树突状细胞、单核细胞、T 细胞亚群和细胞因子的动力学，对人的免疫系统进行了评估。为了充分刺激免疫反应并获得 B 细胞前体 NAML-6 和三阴性乳腺癌 MDA-MB-231 靶向 TCR-T 细胞，我们使用上述灭活细胞处理人源化小鼠，每天两次，每次 7 天。然后，处理人T细胞，进行TCR β-链（TRB）测序分析。在构建了TCR β-链（TRB）序列后，研究了TCR β-链的比例、多样性和免疫特征等特征。 结果 结果表明，治疗后 T 细胞的多样性和克隆性都有所增加。TRBV、TRBJ和V-J组合的优先使用情况和特征也发生了变化。应激还诱导了高度的克隆扩增。肿瘤负荷和存活率分析表明，应激诱导能显著抑制随后输注的活肿瘤细胞的生长，延长人源化小鼠的存活时间。 结论 我们构建了一个个性化人源化小鼠模型来筛选癌症靶向 TCR-T 池。我们的平台提供了癌症靶向 TCR-T 细胞的有效来源，并允许设计患者特异性工程 T 细胞。因此，它有可能极大地促进癌症治疗。
{"title":"Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires","authors":"Yulin Xu, Wei Shan, Qian Luo, Meng Zhang, Dawei Huo, Yijin Chen, Honghu Li, Yishan Ye, Xiaohong Yu, Yi Luo, He Huang","doi":"10.1002/cai2.118","DOIUrl":"https://doi.org/10.1002/cai2.118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer-targeted T-cell receptor T (TCR-T) cells hold promise in treating cancers such as hematological malignancies and breast cancers. However, approaches to obtain cancer-reactive TCR-T cells have been unsuccessful.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints. Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells, and then the expanded cells were applied to establish humanized mice. The human immune system was evaluated according to the kinetics of dendritic cells, monocytes, T-cell subsets, and cytokines. To fully stimulate the immune response and to obtain B-cell precursor NAML-6- and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells, we used the inactivated cells above to treat humanized mice twice a day every 7 days. Then, human T cells were processed for TCR β-chain (TRB) sequencing analysis. After the repertoires had been constructed, features such as the fraction, diversity, and immune signature were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results demonstrated an increase in diversity and clonality of T cells after treatment. The preferential usage and features of TRBV, TRBJ, and the V–J combination were also changed. The stress also induced highly clonal expansion. Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools. Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells. It therefore has the potential to greatly benefit cancer treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552821","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}
Sahil Seth, Runzhe Chen, Yang Liu, Junya Fujimoto, Lingzhi Hong, Alexandre Reuben, Susan Varghese, Carmen Behrens, Tina McDowell, Luisa Solis Soto, Cara Haymaker, Annikka Weissferdt, Neda Kalhor, Jia Wu, Xiuning Le, Natalie I Vokes, Chao Cheng, John V. Heymach, Don L. Gibbons, P. Andrew Futreal, Ignacio I. Wistuba, Humam Kadara, Jianhua Zhang, Cesar Moran, Jianjun Zhang
Background
Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined.
Methods
Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes.
Results
In total, 27 canonical cancer gene mutations were identified, with TP53 the most frequently mutated gene, followed by KRAS. Interestingly, most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs.
Conclusions
We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.
{"title":"Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes","authors":"Sahil Seth, Runzhe Chen, Yang Liu, Junya Fujimoto, Lingzhi Hong, Alexandre Reuben, Susan Varghese, Carmen Behrens, Tina McDowell, Luisa Solis Soto, Cara Haymaker, Annikka Weissferdt, Neda Kalhor, Jia Wu, Xiuning Le, Natalie I Vokes, Chao Cheng, John V. Heymach, Don L. Gibbons, P. Andrew Futreal, Ignacio I. Wistuba, Humam Kadara, Jianhua Zhang, Cesar Moran, Jianjun Zhang","doi":"10.1002/cai2.112","DOIUrl":"https://doi.org/10.1002/cai2.112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 27 canonical cancer gene mutations were identified, with <i>TP53</i> the most frequently mutated gene, followed by <i>KRAS</i>. Interestingly, most <i>TP53</i> and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552053","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}
Wenhua Song, Nan Zhang, Tonglian Lv, Yang Zhao, Guangping Li, Gary Tse, Tong Liu
Background
Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta-analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI-associated myocarditis.
Methods
PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI-associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR-derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies.
Results
Five cohort studies were included (average age 65–68 years; 25.4% female). Of these, four studies were included in the meta-analysis of LGE-related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72–10.19, p = 0.002). A meta-analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43–50.89, p < 0.001) and lower LVEF (WMD = − 8.00%, 95% CI: −13.60 to −2.40, p = 0.005). Notably, T2 value (WMD = −0.23 ms, 95% CI: −1.86 to −1.39, p = 0.779) was not associated with MACE in patients with ICI-related myocarditis.
Conclusions
LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long-term adverse events in patients with ICI-related myocarditis.
{"title":"Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis: A systematic review and meta-analysis","authors":"Wenhua Song, Nan Zhang, Tonglian Lv, Yang Zhao, Guangping Li, Gary Tse, Tong Liu","doi":"10.1002/cai2.109","DOIUrl":"https://doi.org/10.1002/cai2.109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta-analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI-associated myocarditis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI-associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR-derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five cohort studies were included (average age 65–68 years; 25.4% female). Of these, four studies were included in the meta-analysis of LGE-related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72–10.19, <i>p</i> = 0.002). A meta-analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43–50.89, <i>p</i> < 0.001) and lower LVEF (WMD = − 8.00%, 95% CI: −13.60 to −2.40, <i>p</i> = 0.005). Notably, T2 value (WMD = −0.23 ms, 95% CI: −1.86 to −1.39, <i>p</i> = 0.779) was not associated with MACE in patients with ICI-related myocarditis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long-term adverse events in patients with ICI-related myocarditis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556352","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}
Enzhao Zhu, Linmei Zhang, Jiayi Wang, Chunyu Hu, Qi Jing, Weizhong Shi, Ziqin Xu, Pu Ai, Zhihao Dai, Dan Shan, Zisheng Ai
Background
The role of surgery in metastatic breast cancer (MBC) is currently controversial. Several novel statistical and deep learning (DL) methods promise to infer the suitability of surgery at the individual level.
Objective
The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.
Methods
We introduced the deep survival regression with mixture effects (DSME), a semi-parametric DL model integrating three causal inference methods. Six models were trained to make individualized treatment recommendations. Patients who received treatments in line with the DL models' recommendations were compared with those who underwent treatments divergent from the recommendations. Inverse probability weighting (IPW) was used to minimize bias. The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.
Results
In total, 5269 female patients with MBC were included. DSME was an independent protective factor, outperforming other models in recommending surgery (IPW-adjusted hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.19–0.78) and type of surgery (IPW-adjusted HR = 0.66, 95% CI: 0.48–0.93). DSME was superior to other models and traditional guidelines, suggesting a higher proportion of patients benefiting from surgery, especially breast-conserving surgery. The debiased effect of patient characteristics, including age, tumor size, metastatic sites, lymph node status, and breast cancer subtypes, on surgery decision was also quantified.
Conclusions
Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed. This method can facilitate the development of efficient, reliable treatment recommendation systems and provide quantifiable evidence for decision-making.
{"title":"Personalized surgical recommendations and quantitative therapeutic insights for patients with metastatic breast cancer: Insights from deep learning","authors":"Enzhao Zhu, Linmei Zhang, Jiayi Wang, Chunyu Hu, Qi Jing, Weizhong Shi, Ziqin Xu, Pu Ai, Zhihao Dai, Dan Shan, Zisheng Ai","doi":"10.1002/cai2.119","DOIUrl":"https://doi.org/10.1002/cai2.119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The role of surgery in metastatic breast cancer (MBC) is currently controversial. Several novel statistical and deep learning (DL) methods promise to infer the suitability of surgery at the individual level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We introduced the deep survival regression with mixture effects (DSME), a semi-parametric DL model integrating three causal inference methods. Six models were trained to make individualized treatment recommendations. Patients who received treatments in line with the DL models' recommendations were compared with those who underwent treatments divergent from the recommendations. Inverse probability weighting (IPW) was used to minimize bias. The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 5269 female patients with MBC were included. DSME was an independent protective factor, outperforming other models in recommending surgery (IPW-adjusted hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.19–0.78) and type of surgery (IPW-adjusted HR = 0.66, 95% CI: 0.48–0.93). DSME was superior to other models and traditional guidelines, suggesting a higher proportion of patients benefiting from surgery, especially breast-conserving surgery. The debiased effect of patient characteristics, including age, tumor size, metastatic sites, lymph node status, and breast cancer subtypes, on surgery decision was also quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed. This method can facilitate the development of efficient, reliable treatment recommendation systems and provide quantifiable evidence for decision-making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552052","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}
Satoru Sasagawa, Jun Kumai, Toru Wakamatsu, Yoshihiro Yui
Background
Synovial sarcoma (SS) is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics, associated with a poor prognosis due to frequent metastasis to a distant organ, such as the lung. Histone deacetylase (HDAC) inhibitors (HDACis) are arising as potent molecular targeted drugs, as HDACi treatment disrupts the SS oncoprotein complex, which includes HDACs, in addition to general HDACi effects. To provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells, we examined cellular responses to HDACi treatment in combination with two-dimensional (2D) and 3D culture conditions.
Methods
Using several SS cell lines, biochemical and cell biological assays were performed with romidepsin, an HDAC1/2 selective inhibitor. SN38 was concomitantly used as an ameliorant drug with romidepsin treatment. Cytostasis, apoptosis induction, and MHC class I polypeptide-related sequence A/B (MICA/B) induction were monitored to evaluate the drug efficacy. In addition to the conventional 2D culture condition, spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on chemoresistance.
Results
By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells, we observed that responsiveness is diverse in each cell line. In the apoptotic inducible cells, co-treatment with SN38 enhanced cell death. In nonapoptotic inducible cells, cytostasis and MICA/B induction were observed, and SN38 improved MICA/B induction further. As a novel efficacy of SN38, we revealed TWIST1 suppression in SS cells. In the spheroid (3D) condition, romidepsin efficacy was severely restricted in TWIST1-positive cells. We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form, and concomitant SN38 treatment along with romidepsin reproduced the reaction.
Conclusions
The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evidence that concomitant treatment with SN38 can overcome drug resistance to HDACi by suppressing TWIST1 expression.
背景滑膜肉瘤（SS）是一种由SS18-SSX融合基因驱动的软组织肉瘤，具有间质特性，由于经常转移至肺部等远处器官，预后较差。组蛋白去乙酰化酶（HDAC）抑制剂（HDACis）作为强效分子靶向药物应运而生，因为HDACi治疗除了一般的HDACi作用外，还能破坏包括HDACs在内的SS癌蛋白复合物。为了进一步从分子角度证明 HDACi 治疗的优势及其因 SS 细胞微环境诱导的耐药性而产生的局限性，我们结合二维（2D）和三维培养条件研究了细胞对 HDACi 治疗的反应。 方法 利用几种 SS 细胞系，使用 HDAC1/2 选择性抑制剂罗米地辛进行生化和细胞生物学检测。在使用罗米地辛治疗的同时，还使用 SN38 作为改善药物。通过监测细胞凋亡、细胞凋亡诱导和 MHC I 类多肽相关序列 A/B（MICA/B）诱导来评估药物疗效。除了传统的二维培养条件外，还采用了球形培养来评估细胞质微环境对化疗耐药性的影响。 结果 通过监测romidepsin和/或SN38在SS细胞中的细胞行为，我们观察到各细胞系的反应性各不相同。在凋亡诱导型细胞中，与 SN38 联合处理可增强细胞死亡。在非凋亡诱导型细胞中，观察到细胞停滞和 MICA/B 诱导，SN38 进一步改善了 MICA/B 诱导。作为 SN38 的一项新功效，我们发现了 SS 细胞中 TWIST1 的抑制作用。在球形（3D）条件下，罗米地辛在 TWIST1 阳性细胞中的疗效受到严重限制。我们证明，即使在球形细胞中，TWIST1 的下调也能恢复罗米地辛的疗效，而且在罗米地辛治疗的同时，SN38 治疗也能再现这种反应。 结论 目前的研究证明了在二维和三维培养条件下使用 HDACi 治疗 SS 的益处和顾虑，并提供了分子证据，证明同时使用 SN38 治疗可通过抑制 TWIST1 的表达克服对 HDACi 的耐药性。
{"title":"Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma","authors":"Satoru Sasagawa, Jun Kumai, Toru Wakamatsu, Yoshihiro Yui","doi":"10.1002/cai2.113","DOIUrl":"https://doi.org/10.1002/cai2.113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Synovial sarcoma (SS) is an <i>SS18-SSX</i> fusion gene-driven soft tissue sarcoma with mesenchymal characteristics, associated with a poor prognosis due to frequent metastasis to a distant organ, such as the lung. Histone deacetylase (HDAC) inhibitors (HDACis) are arising as potent molecular targeted drugs, as HDACi treatment disrupts the SS oncoprotein complex, which includes HDACs, in addition to general HDACi effects. To provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells, we examined cellular responses to HDACi treatment in combination with two-dimensional (2D) and 3D culture conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using several SS cell lines, biochemical and cell biological assays were performed with romidepsin, an HDAC1/2 selective inhibitor. SN38 was concomitantly used as an ameliorant drug with romidepsin treatment. Cytostasis, apoptosis induction, and MHC class I polypeptide-related sequence A/B (MICA/B) induction were monitored to evaluate the drug efficacy. In addition to the conventional 2D culture condition, spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on chemoresistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells, we observed that responsiveness is diverse in each cell line. In the apoptotic inducible cells, co-treatment with SN38 enhanced cell death. In nonapoptotic inducible cells, cytostasis and MICA/B induction were observed, and SN38 improved MICA/B induction further. As a novel efficacy of SN38, we revealed TWIST1 suppression in SS cells. In the spheroid (3D) condition, romidepsin efficacy was severely restricted in TWIST1-positive cells. We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form, and concomitant SN38 treatment along with romidepsin reproduced the reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evidence that concomitant treatment with SN38 can overcome drug resistance to HDACi by suppressing TWIST1 expression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537677","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}
Shilpa Malakar, Emmanuel Nuah Gontor, Moses Y. Dugbaye, Kamal Shah, Sakshi Sinha, Priya Sutaoney, Nagendra Singh Chauhan
Biosimilars are biological drugs created from living organisms or that contain living components. They share an identical amino-acid sequence and immunogenicity. These drugs are considered to be cost-effective and are utilized in the treatment of cancer and other endocrine disorders. The primary aim of biosimilars is to predict biosimilarity, efficacy, and treatment costs; they are approved by the Food and Drug Administration (FDA) and have no clinical implications. They involve analytical studies to understand the similarities and dissimilarities. A biosimilar manufacturer sets up FDA-approved reference products to evaluate biosimilarity. The contribution of next-generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations. The study shall help to understand the future perspectives of biosimilars for use in gastro-entero-logic diseases, colorectal cancer, and thyroid cancer. They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy, cell treatment, gene therapy, recombinant therapeutic proteins, and personalized medications. Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy. Escherichia coli produces more than six antibodies or antibody-derived proteins to treat cancer such as filgrastim, epoetin alfa, and so on.
生物仿制药是指从生物体中提取或含有生物成分的生物药物。它们具有相同的氨基酸序列和免疫原性。这些药物被认为具有成本效益，可用于治疗癌症和其他内分泌疾病。生物仿制药的主要目的是预测生物相似性、疗效和治疗成本；它们由美国食品和药物管理局（FDA）批准，对临床没有影响。它们涉及分析研究，以了解相似性和不相似性。生物仿制药生产商会建立经 FDA 批准的参照产品，以评估生物仿制药的相似性。下一代测序技术在研究器官肿瘤及其进展方面的贡献正在不断发展，其对癌症患者的影响治疗方法可展示并锁定罕见突变。这项研究将有助于了解生物仿制药在胃肠道疾病、结直肠癌和甲状腺癌中的应用前景。生物仿制药还有助于在临床实践中通过血液和液体活检、细胞治疗、基因治疗、重组治疗蛋白和个性化药物，针对特定器官的基本突变类别和药物原型进行治疗。生物仿制药的衍生物，如曲妥珠单抗和利妥昔单抗等单克隆抗体，是癌症治疗中常用的药物。大肠杆菌可产生六种以上治疗癌症的抗体或抗体衍生蛋白，如 filgrastim、epoetin alfa 等。
{"title":"Cancer treatment with biosimilar drugs: A review","authors":"Shilpa Malakar, Emmanuel Nuah Gontor, Moses Y. Dugbaye, Kamal Shah, Sakshi Sinha, Priya Sutaoney, Nagendra Singh Chauhan","doi":"10.1002/cai2.115","DOIUrl":"https://doi.org/10.1002/cai2.115","url":null,"abstract":"<p>Biosimilars are biological drugs created from living organisms or that contain living components. They share an identical amino-acid sequence and immunogenicity. These drugs are considered to be cost-effective and are utilized in the treatment of cancer and other endocrine disorders. The primary aim of biosimilars is to predict biosimilarity, efficacy, and treatment costs; they are approved by the Food and Drug Administration (FDA) and have no clinical implications. They involve analytical studies to understand the similarities and dissimilarities. A biosimilar manufacturer sets up FDA-approved reference products to evaluate biosimilarity. The contribution of next-generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations. The study shall help to understand the future perspectives of biosimilars for use in gastro-entero-logic diseases, colorectal cancer, and thyroid cancer. They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy, cell treatment, gene therapy, recombinant therapeutic proteins, and personalized medications. Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy. <i>Escherichia coli</i> produces more than six antibodies or antibody-derived proteins to treat cancer such as filgrastim, epoetin alfa, and so on.</p>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537836","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}
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