MedComm – Oncology最新文献

{"title":"The Role of One-Carbon Metabolism in Cancer and Its Therapeutic Significance","authors":"Yuting Jiang,&nbsp;Guoliang Zhou,&nbsp;Qian Zhang,&nbsp;Shengtao Zhou","doi":"10.1002/mog2.70062","DOIUrl":"10.1002/mog2.70062","url":null,"abstract":"<p>Metabolic reprogramming is a hallmark of cancer that sustains uncontrolled proliferation, supports adaptation to hypoxia and nutrient limitation, and shapes antitumor immunity. In this context, one-carbon (1C) metabolism is increasingly recognized as a key integrative pathway that supports proliferative and stress-adaptive programs. 1C metabolism links serine and glycine metabolism with folate and methionine cycles to fuel nucleotide synthesis, methylation, and redox homeostasis. Here, we systematically integrate the biochemical architecture and compartmentalization of 1C metabolism with its cancer-associated rewiring in tumor cells and the tumor microenvironment, spanning biosynthetic, epigenetic, redox, and mitochondrial translation functions, as well as the noncanonical moonlighting functions of metabolic enzymes. We further synthesize emerging evidence for tumor-stroma metabolite exchange and immune-cell metabolic reprogramming and discuss therapeutic opportunities arising from context-dependent 1C vulnerabilities, specifically highlighting the potential of small-molecule inhibitors and dietary interventions. By consolidating mechanistic and translational advances, this review highlights strategies to exploit these specific metabolic fragilities and proposes considerations for biomarker-guided precision anticancer therapy. This synthesis provides a framework for prioritizing targets, interpreting resistance mechanisms, and designing metabolism-informed clinical trials to improve efficacy while mitigating toxicity.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565851","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":"Multifacet Roles of Cellular Senescence in Cancer: Mechanisms and Therapeutic Implications","authors":"Huajie Mao,&nbsp;Wanning Liu,&nbsp;Yuanyuan Su,&nbsp;Yuxuan Ma,&nbsp;Xiaodi Zhao,&nbsp;Yuanyuan Lu","doi":"10.1002/mog2.70060","DOIUrl":"10.1002/mog2.70060","url":null,"abstract":"<p>Cellular senescence plays a complex, dual role in cancer. Senescent cells induce tumor suppression through cell cycle arrest and immune response activation but also secrete pro-inflammatory factors via the senescence-associated secretory phenotype (SASP), which can foster tumor growth, metastasis, and immune evasion. However, the therapeutic potential of targeting senescence mechanisms remains underexplored. This review examines the dual functions of senescent cells in cancer, emphasizing the paradoxical role of the SASP in both promoting tumor progression and modulating immune responses. We explore how SASP factors contribute to tumor growth, metastasis, and immune evasion by reshaping the tumor microenvironment. We then discuss emerging strategies aimed at targeting senescent cells, focusing on approaches for their selective clearance and the modulation of SASP components. These strategies have the potential to enhance the effectiveness of conventional cancer therapies, such as chemotherapy and radiation, by reducing immune-suppression and improving immune surveillance. Additionally, we delve into the growing interest in SASP-targeted immunotherapies, which aim to overcome the immunosuppressive effects of senescent cells and boost antitumor immunity. This review emphasizes the importance of targeting senescence and SASP for developing precision-based cancer therapies, offering new opportunities for next-generation immunotherapy.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565850","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":"Construction of a Prediction Model for Thyroid Nodules Based on Machine Learning","authors":"Siye Gong,&nbsp;Zhicheng Wang,&nbsp;Yulin Xu,&nbsp;Rongli Xie,&nbsp;Jian Fei","doi":"10.1002/mog2.70061","DOIUrl":"10.1002/mog2.70061","url":null,"abstract":"&lt;p&gt;The increasing incidence of papillary thyroid carcinoma (PTC) has intensified debates over its management. The lack of reliable methods for distinguishing indolent from aggressive cases fuels persistent advocacy for surgical intervention [&lt;span&gt;1, 2&lt;/span&gt;]. This controversy underscores a critical gap: the absence of robust preoperative tools to evaluate prognostic factors such as malignancy risk and lymph node metastasis. With the development of technology, artificial intelligence (AI) has played a significant role in medical practice, including predicting trajectories of patients and reducing the risk of misdiagnosis [&lt;span&gt;3-5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The current clinical TI-RADS grading standard classifies category 4 thyroid nodules into subtypes with varying malignancy rates. The clinical value of predicting the benign or malignant status of nodules within this range remains substantial. In this study, we employed machine learning techniques to integrate TI-RADS and clinical indicators to predict the benign or malignant status of TI-RADS category 4 thyroid nodules. Among the models, RF demonstrated superior performance in terms of several metrics, particularly in terms of the overall prediction accuracy.&lt;/p&gt;&lt;p&gt;In this study, we selected a detailed dataset including 1969 patients with thyroid nodules who visited a hospital in Shanghai Ruijin Rehabilitation Hospital. Among these patients, 764 were classified as having TI-RADS category 4 glandular nodules. Rigorous postoperative pathological evaluations were conducted for all participants, and their pathological diagnosis results, along with the relevant clinical indicators, were integrated into the data analysis set.&lt;/p&gt;&lt;p&gt;The average age of the participants was 45.24 years, ranging from 14 to 79 years. In terms of sex composition, 23.69% of the patients were male, totalling 181 cases, while 76.31% were female, totalling 583 cases. All of the thyroid ultrasound images were evaluated by a physician specializing in clinical ultrasound. The evaluation revealed 379 (49.61%) category 4 A nodules, 297 (38.87%) category 4B nodules, and 88 (11.52%) category 4 C nodules, and the final pathological results revealed 448 malignant cases (58.64%) and 316 benign cases (41.36%).&lt;/p&gt;&lt;p&gt;On the basis of the provided description, we evaluated the performance of different machine learning models and their respective hyperparameters, identifying the highest accuracy achieved by each model (Table S1). We assessed the diagnostic performance of these models on the validation set by using a fixed random number seed (Table 1), and we quantified the diagnostic performance metrics of the four models across individual TI-RADS subcategories and performed comparisons against the benchmark malignancy probabilities defined by the TI-RADS classification system (Table S2).&lt;/p&gt;&lt;p&gt;Among the models, RF demonstrated superior performance in terms of several metrics, particularly in terms of the overall prediction accuracy, which was measur","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147563259","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":"Molecular Glue Degraders Redefining Targeted Therapies From Discovery to Therapeutic Applications","authors":"Jinfeng Wen,&nbsp;Jingtian Yu,&nbsp;Wuqiang Wen,&nbsp;Baishan Jiang","doi":"10.1002/mog2.70058","DOIUrl":"10.1002/mog2.70058","url":null,"abstract":"<p>Molecular glue degraders (MGDs) represent an emerging therapy that exploits ubiquitin–proteasome pathways to eliminate otherwise intractable proteins. By stabilizing E3 ligases–target protein interactions, they enable event-driven degradation, advancing targeting of undruggable proteins. Although progress in mechanisms and applications, a coherent framework across disciplines is still lacking. Here, we provide a unified synthesis of MGD mechanisms, including allosteric activation, interface stabilization, and neo-substrate engagement, and delineate the functional diversity of representative ligases such as CRBN, VHL, DCAF15 and RNF126. We further organize emerging applications across oncology, immune dysregulation, metabolic imbalance, and neurodegenerative proteinpathies, highlighting how MGDs modulate disease-relevant pathways. Critical enabling technologies, including chemoproteomics, cryo-electron microscopy (EM), high-throughput screening, and artificial intelligence–driven generative modeling are summarized as key engines accelerating glue discovery and ligase expansion. Together, this review provides a conceptual and technological blueprint for the rational development of next-generation MGDs and aims to unlock transformative therapies for a vast array of diseases rooted in previously undruggable proteins. Furthermore, it offers forward-looking perspectives on overcoming seminal challenges-including enhancing target selectivity, broadening the repertoire of exploitable E3 ligases, and achieving precise spatiotemporal control over degradation.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147568440","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":"The Acetyl-CoA-NLRX1 Axis Acts as a Key Player in Mitophagy and Drug Resistance","authors":"Ping Jin,&nbsp;Biao Hu,&nbsp;Jingwen Jiang,&nbsp;Li Xu","doi":"10.1002/mog2.70055","DOIUrl":"10.1002/mog2.70055","url":null,"abstract":"&lt;p&gt;Zhang et al. reported in &lt;i&gt;Nature&lt;/i&gt; that cytosolic Acetyl-Coenzyme A (AcCoA) directly bound the NOD-like receptor (NLR) family member X1 (NLRX1) to gate mitophagy at the outer mitochondrial membrane [&lt;span&gt;1&lt;/span&gt;]. The authors showed this metabolite-sensing switch shaped Kirsten rat sarcoma viral oncogene homolog (KRAS)-inhibitor responses and contributes to drug resistance.&lt;/p&gt;&lt;p&gt;Mitophagy is a selective form of autophagy that removes damaged or superfluous mitochondria, limiting reactive oxygen species accumulation and preserving bioenergetic fitness. It can be initiated through ubiquitin-dependent routes (classically involving PINK1/Parkin) or receptor-mediated pathways in which OMM proteins recruit autophagy machinery, most notably light chain 3 (LC3)-family proteins, to engulf mitochondria within autophagosomes. The authors expanded this framework by positioning NLRX1 as a metabolite-gated mitophagy receptor, and by identifying cytosolic AcCoA as a dynamic signal that controls whether NLRX1 is “available” to engage the autophagy apparatus [&lt;span&gt;1&lt;/span&gt;]. Mechanistically, cytosolic AcCoA maintained nucleotide-binding and oligomerization (NLRX1) in an autoinhibited state by occupying a conserved pocket within its leucine-rich repeat (LRR) domain. The authors showed that AcCoA binding strengthens intramolecular contacts between the LRR and NACHT domains, effectively “locking” NLRX1 and preventing its association with LC3 (Figure 1). Under conditions in which cytosolic AcCoA declines, this ligand-dependent clamp was released, allowing conformational changes and oligomerization that enable NLRX1 to recruit LC3 and initiate mitophagy. Furthermore, the authors demonstrated that the AcCoA-NLRX1 axis was essential for the KRAS inhibitor-induced mitophagy and promoted adaptive drug resistance. Importantly, NLRX1 sensed dynamic fluctuations in cytosolic AcCoA under metabolic stress (e.g., nutrient deprivation or drug exposure), revealing a signaling function of AcCoA that was independent of acetylation modifications or AMP-activated protein kinase/mammalian target of rapamycin AMPK/mTOR pathways. Collectively, these findings nominated the AcCoA-NLRX1-mitophagy axis as a potential therapeutic vulnerability and suggested a combinatorial strategy to enhance the efficacy of KRAS inhibitors in the context of cancer metabolic rewiring.&lt;/p&gt;&lt;p&gt;AcCoA was a central metabolite involved in energy production, biosynthesis, and key metabolic pathways like the tricarboxylic acid cycle, fatty acid synthesis, and protein acetylation [&lt;span&gt;2&lt;/span&gt;]. In this study, the authors identified cytosolic AcCoA as a key signaling metabolite regulating mitophagy [&lt;span&gt;1&lt;/span&gt;]. In many cells, cytosolic AcCoA is generated largely from citrate exported out of mitochondria and cleaved by ATP citrate lyase (ACLY), while mitochondrial citrate handling is influenced by transporters such as solute carrier family 25 member 1 (SLC25A1), often referred to as the mitochondrial","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146216779","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":"SIRT7 Orchestrates Ligand-Dependent ERα Signaling Rewiring to Drive Tamoxifen Resistance in ERα-positive Breast Cancer","authors":"Yalan Wu,&nbsp;Huixia Liu,&nbsp;Ye Liu,&nbsp;Yanxue Mei,&nbsp;Mengdi Cao,&nbsp;Guo Li,&nbsp;Ronghui Fan,&nbsp;Junfeng Zhang,&nbsp;Langmei Yang,&nbsp;Jieling Liu,&nbsp;Qi Hou,&nbsp;Jinsong Li,&nbsp;Fujun Dai,&nbsp;Baohua Liu,&nbsp;Xiaolong Tang","doi":"10.1002/mog2.70057","DOIUrl":"10.1002/mog2.70057","url":null,"abstract":"<p>Tamoxifen resistance (TAMR) remains a major clinical challenge in the treatment of ERα-positive breast cancer. Although ERα loss and activation of alternative survival pathways are well-known contributors, the mechanisms underlying ERα dysregulation and signaling rewiring remain incompletely understood. Here, we show that SIRT7 is markedly upregulated in TAMR cells and patient-derived xenografts (PDXs), and that its depletion significantly suppresses TAMR phenotypes. Mechanistically, SIRT7-mediated deacetylation of ERα at lysines 302 and 303 facilitates its dissociation from the HSP90 chaperone complex and subsequent recognition by the E3 ubiquitin ligase CHIP, resulting in K48-linked polyubiquitination and proteasomal degradation of ERα. This mechanism underlies the context-dependent dual role of SIRT7: In tamoxifen-sensitive breast cancer, SIRT7 suppresses canonical ERα signaling and restrains tumor growth by accelerating ERα degradation, which promotes the development of estrogen-independent progression. By contrast, under tamoxifen treatment, the interaction between SIRT7 and ERα is enhanced, which unexpectedly redirects deacetylated ERα toward activation of EGFR signaling and thereby drives therapeutic resistance. Notably, pharmacological inhibition of SIRT7 with compound 97491 induces pronounced regression of TAMR-derived xenografts. Collectively, these findings establish SIRT7 as a central regulator of ERα signaling and a promising therapeutic target for overcoming endocrine resistance in breast cancer.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256375","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":"Metabolic Reprogramming of the Pre-Metastatic Niche: A Sweet Spot for Anti-Tumor Immunity","authors":"Xuan Zhang,&nbsp;Xinghua Long","doi":"10.1002/mog2.70056","DOIUrl":"10.1002/mog2.70056","url":null,"abstract":"&lt;p&gt;In a research article published in Cell, Wu et al. revealed a critical paradox: Glucose restriction inhibits primary tumor growth while promoting metastasis [&lt;span&gt;1&lt;/span&gt;]. The research systematically delineates the mechanism by which glucose deprivation promotes lung metastasis, laying the theoretical foundation for combined metabolic reprogramming and immunotherapy.&lt;/p&gt;&lt;p&gt;The proliferation of tumor cells is highly dependent on glucose metabolism [&lt;span&gt;2&lt;/span&gt;]. Previous studies have demonstrated that targeting glucose metabolism can activate apoptotic signaling pathways in cancer cells, thereby inhibiting malignant tumor proliferation [&lt;span&gt;3&lt;/span&gt;]. However, metastasis, rather than primary tumor growth, is the principal cause of cancer-related deaths. Two key findings were achieved: First, in distant metastatic sites such as the lungs, glucose deprivation can cause macrophage-mediated natural killer (NK) cell exhaustion through the poliovirus receptor (PVR)-T cell immunoreceptor with Ig and ITIM domains (TIGIT) axis, forming a pre-metastatic niche (PMN) conducive to tumor metastasis; Second, in primary tumors, there is a regulatory relationship between glucose deprivation and exosomal tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and it is revealed that exosomal TRAIL has a non-classical effect.&lt;/p&gt;&lt;p&gt;Genetic Set Variation Analysis (GSVA) of clinical data showed a significant association between low glucose metabolism and increased 2-year postoperative recurrence rates across 15 cancer types, most notably in hepatocellular carcinoma (HCC) [&lt;span&gt;1&lt;/span&gt;]. In this study, models of glucose restriction were established using a low-carbohydrate (LC) diet and impaired glucose metabolism. Using multiple tumor mouse models, it was concluded that although glucose deficiency induced by an LC diet inhibits primary tumor growth, it unexpectedly elevated the risk of lung metastasis (Figure 1A). Conversely, glutamine deprivation did not significantly promote metastasis in HCC. Notably, unlike high-carbohydrate (HC) diets, lung metastasis induced by LC diets was unrelated to increased primary tumor volume [&lt;span&gt;1&lt;/span&gt;]. Further research suggested that enhanced metastasis under glucose restriction was attributable to PMN formation rather than enhanced invasiveness of cancer cells.&lt;/p&gt;&lt;p&gt;The formation of the PMN in distant organs is a critical step in the development of metastasis, as it creates an environment that supports the colonization of tumor cells. While previous studies have primarily focused on pro-tumor factors such as fibronectin and vascular endothelial growth factor [&lt;span&gt;4&lt;/span&gt;], the authors adopted a novel metabolic perspective to investigate the role of glucose deprivation in the establishment of the PMN. They found that glucose deprivation in the primary tumor established PMNs in the lungs, characterized by macrophage-dependent NK cell exhaustion and functional impairment. Notably, the LC diet only slightly","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147997","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":"Cancer Comorbidities: Clinical Impacts, Mechanistic Insights, and Management Strategies","authors":"Taoxing Peng,&nbsp;Siyi Chen,&nbsp;Xin He,&nbsp;Yuxin Yang,&nbsp;Yuexiang Ren,&nbsp;Yuxuan Sun,&nbsp;Fuli Shi,&nbsp;Yangfeng Lv,&nbsp;Xiangqiong Wen,&nbsp;Yujian Wen,&nbsp;Peng Yu,&nbsp;Weizhu Liu,&nbsp;Qiongfeng Chen,&nbsp;Xianhe Yang,&nbsp;Shan Xu,&nbsp;Jianming Li","doi":"10.1002/mog2.70052","DOIUrl":"10.1002/mog2.70052","url":null,"abstract":"<p>Cancer patients often have comorbidities that complicate treatment and worsen outcomes. Despite ongoing discussions, the interactions between comorbidities and cancer remain insufficiently understood. In addition, a widely accepted consensus on the document, assessment, and management of these comorbidities has not yet been established. This review aims to systematically synthesize current knowledge and propose a comprehensive framework for addressing these gaps. It summarizes the epidemiology and analyzes the clinical impacts of comorbidities on cancer patients, emphasizing the critical role of effective management of cancer comorbidities. It further examines key management challenges, including gaps in mechanisms and clinical evidence, the lack of precise assessment tools, limited management frameworks, and underdeveloped multidisciplinary collaborations. To address the complex interactions between cancer and comorbidities, this review proposes the establishment of Oncology-Comorbidity as a novel discipline and Oncology-Comorbidity Interaction Pathology as a theoretical framework. The assistance of artificial intelligence and real-world data, together with effective multidisciplinary collaborations, is emphasized as an essential management strategy. Comprehensive, patient-centered Life-Course Cohort Studies are identified as indispensable tools. Ultimately, this review aims to advance the understanding of cancer-comorbidity interactions, provide a roadmap for optimizing comorbidities management, and offer an effective pathway to improve prognosis and quality of life for cancer patients.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146139244","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":"RNA-Binding Proteins and Ferroptosis in Cancer: Mechanism and Therapeutic Implications","authors":"Linlin Chang,&nbsp;Bin Lu,&nbsp;Haotian Shang,&nbsp;Wanjing Ding,&nbsp;Chunhua Wei,&nbsp;Xiaotian Qi,&nbsp;Pengxing He","doi":"10.1002/mog2.70053","DOIUrl":"10.1002/mog2.70053","url":null,"abstract":"<p>Ferroptosis is a regulated, iron-dependent form of cell death that has emerged as a promising therapeutic target for multiple cancers. However, its clinical translation faces significant challenges, particularly regarding precision and safety for cancer patients. Recent studies have identified RNA-binding proteins (RBPs) as novel regulators of tumor ferroptosis, extending beyond the established biochemical hallmarks and core defense mechanisms of ferroptosis. This review focuses on the core machinery of ferroptosis and the canonical functions of RBPs in cancer biology. We further present evidence demonstrating that RBPs play a critical role in coordinating iron, lipid, and amino acid metabolism to influence ferroptosis, highlighting the complex interplay between RBPs and ferroptotic processes. Building on these insights, we explore therapeutic opportunities targeting the RBP-ferroptosis axis from three perspectives: small molecules, synthetic lethality strategies, and drug delivery systems. Finally, we discuss the challenges and future prospects of RBP-based ferroptosis therapeutic strategies in cancer. Overall, this review underscores the significant role of RBPs in tumor ferroptosis and lays the groundwork for precision oncology approaches guided by ferroptosis, moving beyond the classical biochemical hallmarks and core defense systems.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140183","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":"Aging-Derived Alterations in Genomic, Immune, and Metabolic Networks: Implications for Cancer Development and Therapy","authors":"Qi Wang,&nbsp;Xue Sun,&nbsp;Xinhao Han,&nbsp;Xingda Zhang,&nbsp;Wenzheng Wang,&nbsp;Hongbin Wang,&nbsp;He Ren,&nbsp;Lina Gu","doi":"10.1002/mog2.70054","DOIUrl":"10.1002/mog2.70054","url":null,"abstract":"<p>Aging is the most potent independent risk factor for cancer initiation and progression, with these processes interacting through complex multi-level biological networks. While current research has identified key pathways, systematic integration of their synergistic effects and actionable clinical strategies remains underexplored. This review examines the complex nonlinear relationship between age and cancer risk, focusing on immune-cancer imbalance and late-stage rebalancing phenomena that accompany aging. It introduces the novel concept of premature cancer, emphasizing its distinct molecular features and microenvironment. During aging, genomic instability, dysregulated epigenetic modifications, immune senescence, and metabolic reprogramming are key biological changes that destabilize the aging-associated tumor microenvironment, fostering conditions conducive to cancer initiation and progression. The paper further explores the gene-immune-metabolic regulatory network formed through multidimensional interactions of these mechanisms, shedding light on how aging promotes cancer through this network. Additionally, translational therapeutic strategies, such as senescent cell eliminators and immunometabolic interventions, are discussed, with attention to challenges like the toxicity of senescent cell eliminators, the double-edged sword effect of nicotinamide adenine dinucleotide (NAD⁺) supplementation, and treatment resistance. This work provides new insights for precision prevention and treatment of age-related cancers, offering a foundation for advancing mechanistic research and promoting aging.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058032","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}