MedComm – Oncology最新文献

{"title":"Cancer stem cells: Signaling pathways and therapeutic targeting","authors":"Joyeeta Talukdar,&nbsp;Tryambak P. Srivastava,&nbsp;Om S. Sahoo,&nbsp;Abhibroto Karmakar,&nbsp;Avdhesh K. Rai,&nbsp;Anupam Sarma,&nbsp;Gayatri Gogoi,&nbsp;Mohammed S. Alqahtani,&nbsp;Mohamed Abbas,&nbsp;Ruby Dhar,&nbsp;Subhradip Karmakar","doi":"10.1002/mog2.62","DOIUrl":"https://doi.org/10.1002/mog2.62","url":null,"abstract":"<p>Cancer stem cells (CSCs) constitute a minority cell population characterized by unbounded proliferative potential in both solid and hematological cancers. Despite sharing key stem cell attributes, CSCs possess unique traits, including the initiation and propagation of tumors and resistance to conventional therapies. The purpose of this review is to delve into the origins and fundamental characteristics of CSCs, emphasizing their role in tumor growth and metastasis. The focus extends to unraveling cellular signaling pathways driving oncogenic processes and understanding aberrant cellular crosstalk crucial for targeted cancer therapies. Beginning with an exploration of CSC properties and behavior, we progress to dissecting the cellular signaling network that fuels oncogenic pathways. The discussion spans the inception of CSCs, their survival strategies, and adaptation to new environments. We then transit to recent therapeutic advancements targeting CSCs, culminating in an exploration for precise therapeutic targeting. This review henceforth, underscores the vital significance of comprehending CSCs in cancer progression and treatment resistance. By unraveling the complex signaling pathways and survival mechanisms unique to CSCs, it paves the way for targeted therapeutic strategies that hold immense promise in enhancing cancer treatment efficacy while minimizing collateral damage.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101183","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":"Application of machine learning to classify cancers of unknown primary","authors":"Shuvam Sarkar,&nbsp;Daniel T. Baptista-Hon","doi":"10.1002/mog2.63","DOIUrl":"https://doi.org/10.1002/mog2.63","url":null,"abstract":"<p>A recent study by Moon et al.<span>¹</span> published in Nature Medicine highlights the role of OncoNPC, a machine learning tool, in diagnosing cancers of unknown primary (CUP). The study offers an insight into the efficacy and accessibility of OncoNPC over traditional diagnostic tools and highlights the wider implications of machine learning technologies in delivering precision medicine.</p><p>The emergence of targeted immunotherapy over the past decade has led to a paradigm shift in clinical oncology. The efficacy of therapeutic agents in treating cancers such as chronic myeloid leukemia and HER2-positive breast cancer, for example, are now well established.<span>²</span> However, CUPs, metastatic diseases where the primary tumor could not be identified present a significant challenge in this new era of precision medicine. CUPs account for 3%–5% of cancer diagnoses and present significant challenges in providing targeted therapy due to diagnostic uncertainty, and limited therapeutic targets.<span>³</span> Indeed, the mortality rate in patients with CUPs is up to 80% at 12 months postdiagnosis.<span>⁴</span></p><p>Several authors have hypothesized pathological mechanisms that might underlie CUPs. Lopez-Lazaro<span>⁵</span> reconciled existing research on stem cells driving tumorigenesis by suggesting CUPs may occur as a result of stem cell migration followed by malignant transformation. This could, in theory, present as metastatic cancer in the absence of a clear primary tumor. Alternative studies have suggested CUPs occur from early dissemination of a primary tumor resulting in rapidly progressive metastatic disease.<span>⁴</span> This would account for the significant mortality rate associated with CUPs as early dissemination could increase metastatic burden and limit therapeutic interventions.</p><p>Current approaches for investigating CUPs focus primarily on immunohistochemistry (IHC) techniques or molecular profiling of tumor samples. Interpretation of IHC results can be inherently subjective. Studies using IHC techniques to investigate CUPs were only able to suggest a primary tumor in 25% of patients.<span>⁶</span> Molecular profiling compromises several techniques such as whole genome sequencing or gene expression analysis to determine the primary tumor based on the molecular characteristics of tumor cells. The efficacy of these methods remains unclear, however, as implementation into clinical practice is often limited by cost-effectiveness.</p><p>Moon et al utilized next-generation sequencing (NGS) data within this study to guide genomic profiling of CUPs.<span>¹</span> NGS elicits a cellular genetic profile by simultaneously analyzing millions of fragments of DNA. This method is relatively cost-effective and significant tumor NGS data already exists.<span>⁷</span> This study therefore uses NGS data in concordance with electronic health ","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.63","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138739871","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":"Cellular senescence: A potential mode of circular RNAs regulating prostate cancer","authors":"Yunpeng Li,&nbsp;Aoyu Fan,&nbsp;Yunyan Zhang,&nbsp;Ziyi Guo,&nbsp;Wei Meng,&nbsp;Wei Pan,&nbsp;Zhongliang Ma,&nbsp;Wei Chen","doi":"10.1002/mog2.61","DOIUrl":"https://doi.org/10.1002/mog2.61","url":null,"abstract":"<p>Cellular senescence is a state characterized by permanent cell cycle stoppage, which has long been viewed as a protective mechanism against neoplasia. However, accumulating evidence reveal that cellular senescence variously stimulates tumorigenesis and malignant progression in certain contexts. Senescence-associated secretory phenotype (SASP) is a crucial feature of senescent cells and the main way they function. Prostate cancer (PCa) is apparently an age-related tumor with a high prevalence in the elderly. With the aggravation of population aging the morbidity of PCa continues to rise. And with the progress of the disease, most patients eventually develop castration-resistant PCa (CRPC) or drug resistance, which poses a challenge for the treatment of PCa and aggravates the burden on patients and society. Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs formed by back-splicing of pre-mRNAs. Characterized by special covalently closed circular structure, they play important regulatory roles in various tumors. Numerous studies have revealed that circRNAs can regulate PCa and cellular senescence in diverse ways. This review explores a potential mode that circRNAs regulate PCa, reveales a significant mechanism of tumorigenesis and progression for PCa, suggesting a new strategy for PCa research.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.61","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138634351","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":"Novel insights into HBV-hepatocellular carcinoma at single-cell sequencing","authors":"Dandan Yin,&nbsp;Tao Zhou,&nbsp;Xuyang Xia,&nbsp;Chang Han,&nbsp;Zhaoqian Liu,&nbsp;Qiu Li,&nbsp;Yang Shu,&nbsp;Heng Xu","doi":"10.1002/mog2.60","DOIUrl":"https://doi.org/10.1002/mog2.60","url":null,"abstract":"<p>A significant proportion of hepatocellular carcinoma (HCC) is pathologically associated with hepatitis B virus (HBV) infection, followed by unsatisfied clinical outcomes. The increasing unmet need for HBV-associated hepatocellular carcinoma (HBV-HCC) treatment drives to deeper understand the role of the intricate immune microenvironment, tumor cell plasticity and dynamics of tumor evolution in HBV-associated hepatic carcinogenesis. Thus, a comprehensive understanding of cross-talk between HBV, host cells, and tumor microenvironment is of fundamental importance for identifying immune imbalance and heterogeneity in HBV-HCC. Over the past 5 years, the application of single-cell RNA sequencing (scRNA-seq) in the understanding of heterogeneity and dynamics of immune cells, clonal evolution, and cancer stem cell (CSC) subsets of tumor cells has established a landscape for HBV-HCC tumor ecosystem. Novel insights into anatomizing immune escape mechanisms and tumor drug resistance have remarkably facilitated the revolution of HBV-HCC clinical treatment. Here, we provided a summary of HCC at single-cell resolution and details on the basic workflow, limitations, and improvements of scRNA-seq. The review highlights novel insights derived from scRNA-seq on advances in the immune microenvironment and tumor heterogeneity of HBV-HCC.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.60","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570982","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":"COVID-19 and cancer: Dichotomy of the menacing dilemma","authors":"Mrinal K. Ghosh,&nbsp;Shaheda Tabassum,&nbsp;Malini Basu","doi":"10.1002/mog2.58","DOIUrl":"https://doi.org/10.1002/mog2.58","url":null,"abstract":"<p>The coronavirus disease 2019 (COVID-19) pandemic brought about unprecedented challenges to global healthcare systems. Among the most vulnerable populations are cancer patients, who face dilemmas due to their compromised immune systems and the intricate interplay with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This comprehensive review delves into the multifaceted relationship between COVID-19 and cancer. Through an analysis of existing literature and clinical data, this review unravels the structural intricacies of the virus and examines its profound implications for cancer patients, thereby bridging the knowledge gap between virology and oncology. The review commences with an introduction regarding the COVID-19 pandemic and cancer. It then transitions into a detailed examination of the SARS-CoV-2 virus and its variants such as Alpha (PANGO lineage B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529 lineage). Subsequently, an insightful analysis of the impact of COVID-19 on major cancer types (viz., Lung, Colon, Brain, and gastrointestinal cancer) is elaborated. Finally, the therapeutic avenues, oncological care, and management are discussed. The nexus between COVID-19 and cancer adds a layer of complexity to patient care, emphasizing the importance of tailored approaches for those grappling with both conditions. Amid the landscape defined by the evolving viral strains, this review navigates through the multifaceted implications of COVID-19 on cancer patients and underscores the significance of integrating virology and oncology.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.58","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138468424","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":"Systematic analysis of markers for T-cell differentiation revealing CD95 as a novel biomarker for prognosis and immunotherapeutic efficacy in colon cancer","authors":"Yuxin Shi,&nbsp;Jie Mei,&nbsp;Rui Hou,&nbsp;Hao Wang,&nbsp;Junli Ding,&nbsp;Junying Xu","doi":"10.1002/mog2.57","DOIUrl":"https://doi.org/10.1002/mog2.57","url":null,"abstract":"<p>Colon cancer is the third most frequently diagnosed cancer worldwide. Considerable progress has been made in the therapeutic strategies and the accuracy of predicting the patients' prognosis. In the past decade, immunotherapy, represented by programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) signaling inhibitors have made remarkable advances in many solid tumors, but limited effect in colon cancer. In particular, colon cancer demonstrates a remarkably poor response to immunotherapy compared with other cancers, with a notable exception of tumors harboring high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR).<span>¹</span> MSI-H or dMMR tumors are characterized by high mutational/neo-antigen burden, and an inflammatory tumor microenvironment with abundant tumor-infiltrating lymphocytes (TILs).<span>²</span> Although better efficacy could be achieved in a small group of patients with MSI-H or dMMR tumors, a proportion of other patients could benefit from immunotherapy. Thus, more appropriate biomarkers are needed to be discovered to predict the patients' prognosis and immunotherapeutic efficacy.</p><p>Different T-cell subsets in the tumor immune microenvironment (TIME) are closely related to the antitumor response and the prognosis of tumor patients. Tumor-specific CD8⁺ T cells are the core cellular components that exert antitumor effects in TIME, by recognizing specific receptors on the tumor surface and secreting cytokines or via the Fas/FsaL pathway. Multiple T-cell subsets are characterized by respective differentiation markers. Currently, with the deepening research of T-cell subsets, the detection of relevant immune indicators and the formulation of therapeutic schedules have attracted increasing clinical attention. By monitoring the expression of T-cell differentiation markers in patients with colon cancer, the benefit of patients receiving immunotherapy can be further evaluated, thus providing a theoretical basis for judging the clinical prognosis and designing more feasible treatment plans.</p><p>In this research, we systematically analyzed the prognostic values of multiple markers for different T-cell subsets<span>³</span> using the Cancer Genome Atlas (TCGA) data set. Among all markers for different T cell subsets, we found that CD95 expression was correlated with better overall survival (OS) and progression-free survival (PFS), while BCL2 and CD122 were only correlated with PFS (Figure 1A,B). Therefore, CD95 was speculated to be associated with prognosis in colon cancer and was selected for further investigation and validation. The analysis of single-cell RNA-sequencing data set confirmed that CD95 was highly expressed in immune cells, especially in various T-cell subtypes (Figure S1A–C). CD95 is a member of the tumor necrosis factor receptor (TNF-R) superfamily and treated as characteristic marker of memeroy cells. It could also be used as the","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.57","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138146306","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":"Development of covalent inhibitors: Principle, design, and application in cancer","authors":"Lang Zheng,&nbsp;Yang Li,&nbsp;Defa Wu,&nbsp;Huan Xiao,&nbsp;Shilong Zheng,&nbsp;Guan Wang,&nbsp;Qiu Sun","doi":"10.1002/mog2.56","DOIUrl":"10.1002/mog2.56","url":null,"abstract":"<p>Covalent inhibitors have been a rapidly growing field in drug discovery due to their therapeutic potential and unique advantages in cancer therapy. As opposed to noncovalent inhibitory drugs, covalent inhibitors reversibly or irreversibly modify proximal nucleophilic amino acid residues on proteins, aiming to selectively recognize and bind to protein targets and addressing some of the challenges faced by noncovalent drugs. Most successful targeted covalent inhibitors depend primarily on binding-site cysteine residues, but this has limitations for certain protein targets that lack targetable cysteine residues. Recently, the rational design of covalent inhibitors or covalent probes targeting other nucleophilic residues, such as lysine, tyrosine, serine, has turned out to be another promising strategy for cancer therapy. Thus, the development of novel strategies to extend the scope of covalent binding and improve the binding properties is required. This review gives a summary of the development of covalent inhibitors targeting noncysteine from different aspects, including target identification, structure–activity relationships, drug discovery strategies, and binding properties, in the hope of providing a scientific reference for future covalent drug discovery as a means of expanding research in cancer therapy.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.56","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135928320","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":"Viral vector-based cancer treatment and current clinical applications","authors":"Lingwan Xie,&nbsp;Yinze Han,&nbsp;Yuanzhi Liu,&nbsp;Yanmei Zhou,&nbsp;Jiao Yu,&nbsp;Albrecht von Brunn,&nbsp;Jian Lei","doi":"10.1002/mog2.55","DOIUrl":"10.1002/mog2.55","url":null,"abstract":"<p>Owing to the limitations of conventional cancer therapies, including chemotherapy, radiotherapy, and surgery, gene therapy has become a prominent strategy for cancer treatment over the past few decades. Gene therapy is a medical approach for targeting and destroying cancer cells by delivering exogenous genes into the target cancerous cells or surrounding tissues. However, successful delivery of foreign genes into target cells and tissues remains a key issue in such therapy. Efficient gene delivery systems would undoubtedly be important for improving the medical outcomes of gene therapy. With genetic modifications, viral vectors can target specific cells with high gene transduction efficiency, thus, the use of viral vectors is a promising technology for improving foreign gene delivery. Currently, four viral vectors—adenovirus, adeno-associated virus, herpes simplex virus, and retrovirus—are dominantly being investigated and used in preclinical and clinical trials. In this review, we provide an overview of the mechanisms and latest applications of the four above-mentioned viral vectors, and summarize the current development of several other viral vectors. In addition, we discuss the challenges and provide insights into future development of viral vectors in cancer treatment.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.55","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136134896","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":"MUC16 C terminal fragment activates YAP1 through Src signaling to promote gallbladder cancer growth","authors":"Kun Fan,&nbsp;Jiwen Wang,&nbsp;Kaihua Zhu,&nbsp;Xiaojian Ni,&nbsp;Sheng Shen,&nbsp;Zijun Gong,&nbsp;Xiaobo Bo,&nbsp;Changcheng Wang,&nbsp;Xi Cheng,&nbsp;Cheng Zhang,&nbsp;Tao Suo,&nbsp;Han Liu,&nbsp;Xiaoling Ni,&nbsp;Houbao Liu","doi":"10.1002/mog2.54","DOIUrl":"https://doi.org/10.1002/mog2.54","url":null,"abstract":"<p>The Hippo pathway is crucial to organ size control and its dysregulation contributes to tumorigenesis. The aberrant activation of YAP1 was identified in gallbladder cancer (GBC). However, the underlying mechanism and role in GBC remains unclear. The C terminal fragment of Mucin16, also known as carbohydrate antigen 125 (CA125) encoded product, MUC16c, plays extensive roles in tumor initiation and development. Our study showed that MUC16c binding with 14-3-3ε disrupted the interaction of 14-3-3ε and phosphorylated yes-associated protein 1 (YAP1), which led to the activation of YAP1 in GBC. Furthermore, MUC16c decreased the phosphorylation of YAP1 at serine 397 (ser397) by inhibiting LATS1, which upregulated YAP1 protein stability. Interestingly, there was a potential Src kinase site in the MUC16c fragment. The MUC16c_del15Y polypeptides with the deletion of the Src kinase site promoted the interaction of YAP1 with 14-3-3ε and downregulated the YAP1 protein levels. Consistently, SU6656, a Src kinase inhibitor also blocked the activation of YAP1 by MUC16c. The MUC16c_del15Y polypeptides decreased GBC cell proliferation in vitro and the growth of xenograft tumors in vivo. Our study revealed the underlying mechanism of the activation of MUC16c on YAP1 mediated by Src signaling and the antitumor effect of MUC16c_del15Y, providing a potential target for GBC therapy.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.54","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50151876","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":"p38 mitogen-activated protein kinase: Functions and targeted therapy in diseases","authors":"Qinwen Zheng,&nbsp;Shutong Li,&nbsp;Aoxue Wang,&nbsp;Man Zhe,&nbsp;Panpan Yang,&nbsp;Yongya Wu,&nbsp;Min Zhao,&nbsp;Yumeng Zhu,&nbsp;Yi Luo,&nbsp;Guan Wang,&nbsp;Liang Ouyang","doi":"10.1002/mog2.53","DOIUrl":"https://doi.org/10.1002/mog2.53","url":null,"abstract":"<p>P38 mitogen-activated protein kinase (p38MAPK) is a multifunctional protein kinase that plays an important role in human normal physiological activities and a variety of major diseases, and its signaling pathway affects a variety of regulatory factors in vivo, which is related to cell cycle, survival, metabolism, and differentiation. The four subtypes of p38MAPK have significant differences in their distribution, content, and effects in the body. The inhibitors of the four subtypes play potential roles in regulating cancer, neurodegenerative diseases, inflammation, and cardiovascular diseases, making it an attractive target for drug development. So far, an increasing number of p38MAPK inhibitors have been developed for targeted therapy in diseases, among which some representative compounds have entered clinical trials. Therefore, this review aims to provide a summary of the structural characteristics, signaling pathways of P38MAPK and the relationship between p38MAPK and disease, along with an overview of the binding modes and structure–activity relationships of small molecule inhibitors targeting four p38MAPK subtypes, and summarizes the challenges about the development of p38MAPK inhibitors, hoping to provide a valuable reference for the development and application of novel inhibitors.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.53","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50145635","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}