MedComm – Oncology最新文献

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.

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.

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.

Local anesthetics, such as lidocaine and ropivacaine, are fundamental to perioperative pain management. Beyond anesthesia, growing evidence indicates that local anesthetics may exert anticancer effects, potentially improving long-term oncologic outcomes by modulating tumor cell behavior and the perioperative environment. Surgery itself could promote metastasis via inflammatory and immunosuppressive pathways. However, the specific role and full therapeutic potential of local anesthetics in countering these effects are not fully defined. This review systematically synthesizes current understanding of the direct and indirect antitumor mechanisms of local anesthetics. We detail their direct inhibition of cancer cell proliferation through the induction of apoptosis and cell cycle arrest. The review also analyzes their indirect effects on the tumor microenvironment, which include enhancing antitumor immunity, attenuating surgery-induced stress and systemic inflammation, and inhibiting angiogenesis. We explore the potential synergy between local anesthetics and established cancer therapies, such as immunotherapy and targeted agents. Finally, the clinical evidence was appraised critically, discussing observational studies and the limited interventional trials linking regional anesthesia to improved survival, while addressing heterogeneity and confounding factors. By synthesizing mechanistic insights with clinical data, this review establishes a foundation for future research and highlights the translational potential of local anesthetics as adjuncts in perioperative cancer care.

Tumor dormancy is a clinically challenging but physiologically significant aspect of cancer development, characterized by disseminated tumor cells that persist in non-proliferative, quiescent state and frequently serving as a risk factor of recurrence. Although extensive progress has been made in understanding cancer progression and metastasis, strategies for reliably detecting and eliminating dormant tumor cells remain limited. This review aims to evaluate the current understanding of the molecular mechanisms underlying tumor dormancy, cellular quiscence, angiogenic processes, immune surveillance, and the complex roles of the tumor microenvironment, including extracellular matrix remodeling, metabolic adaptation and niche protection in tumor dormancy. Particular attention is given to the challenges associated with detecting and eliminating dormant cells, because these cells exhibit resistance to conventional therapies and reveal evasion of immune responses. Furthermore, we highlight peptide-based strategies as promising platforms for detection, modulation and elimination of dormant tumor cells. These include tumor-penetrating peptides, peptide-drug conjugates, self-assembling peptide nanostructures, and hydrogel–based delivery systems designed to disrupt dormancy-maintaining niches or sensitize dormant cells to therapeutic intervention. The review also provides a summary of recent preclinical and clinical developments in peptide-based treatments and outlines approaches to overcome translational challenges in targeting tumor dormancy. By integrating advances in peptide engineering with the biological principles of tumor dormancy, this review underscores the potential of peptide-based platforms to improve therapeutic outcomes and reduce cancer recurrence.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) interact with multiple immune cells, such as T cells, macrophages, neutrophils, and other immune cells, to display both antitumor or protumor effects. Despite enormous progress in immunotherapy, the CAF-associated resistance of immunotherapy is still urgent to be solved. In this review, we summarize the origins and heterogeneity of CAFs in the TME, including the subpopulations of CAFs and their biological function. Then we discuss the communications between CAFs and tumor-associated macrophages, T lymphocytes, tumor-associated neutrophils, and other immune cells. CAFs cannot only recruit immune cells in the TME, but also trigger polarization, proliferation, infiltration of immune cells, thereby promoting tumor progression. Inversely, some immune cells promote the recruitment, transdifferentiation, and proliferation of CAFs. We also focus on the current progress in therapeutic strategies targeting CAF-elimination, CAF-reprograming, downstream signaling blockade, and CAF-induced extracellular matrix barrier elimination to enhance the efficacy of immunotherapy and related clinical trials. Overall, we aim to provide the conceptions of CAF-immunocyte crosstalk in the TME and application of immunotherapy, paving the way for the development of precise and individualized strategies through clarifying the interaction between CAFs and immunocytes.

Imatinib (IM) is the first-line therapy for high-risk gastrointestinal stromal tumor (GIST) patients; however, over 50% of those with advanced stage or metastasis develop IM resistance within 2 years, and effective strategies to overcome this resistance remain elusive. In this study, we identified that decreased N6-methyladenosine (m6A) modification by the demethylase FTO regulated GIST progression and IM resistance. Long noncoding RNA XIST (XIST) was identified as the main demethylated RNA by FTO in GIST. FTO leaded to a decrease in m6A modification at the 10517-10633 site of XIST, thereby protecting it from degradation mediated by YTHDF2's recognition and binding. Stabilized XIST enhanced IM resistance by acting as a posttranscriptional regulator of KIT, the primary oncogenic driver in GIST. In vitro and in vivo functional assays confirmed the roles of both FTO and XIST in promoting GIST progression and IM resistance. Importantly, pharmacological inhibition of FTO using FB23-2 effectively restored IM sensitivity in murine xenograft models of GIST. Together, our findings establish a mechanistic link among FTO-mediated m6A demethylation, XIST stabilization, and posttranscriptional regulation of KIT in GIST. These insights highlight the therapeutic potential of targeting m6A-FTO axis to overcome IM resistance in GIST treatment.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, accounting for approximately 50% of global lung cancer-related mortality, which underscores the urgent need for identifying novel biomarkers and therapeutic targets. Long noncoding RNAs (lncRNAs) have been increasingly recognized as pivotal regulators in cancer development; however, the specific function of lncRNA small nucleolar RNA host gene 5 (SNHG5) in LUAD remained unclear. This study aimed to investigate the clinical significance, biological roles, and molecular mechanisms of SNHG5 in LUAD pathogenesis. Through integrated bioinformatics analysis and experimental validation, we found that SNHG5 was significantly upregulated in LUAD tissues and cell lines. Functional in vitro and in vivo assays—including gain-/loss-of-function studies, luciferase reporter assays, RNA immunoprecipitation, co-immunoprecipitation, and tumor xenograft models—demonstrated that SNHG5 promoted malignant phenotypes by acting as a competing endogenous RNA (ceRNA) for miR-363-3p. This sponge activity elevated the expression of ubiquitin-specific peptidase 28 (USP28), which in turn stabilized β-catenin and activated oncogenic signaling. Rescue experiments confirmed the functional importance of the SNHG5/miR-363-3p/USP28/β-catenin axis. In conclusion, these results indicate that SNHG5 drives LUAD progression through a novel ceRNA mechanism, highlighting its potential as both a prognostic biomarker and a therapeutic target.

Metabolic reprogramming is a core hallmark of malignant tumors. It facilitates the rapid growth of tumor cells and significantly modulates antitumour immune responses through metabolic interactions, affecting the success of immunotherapy. Despite recent breakthroughs in immunotherapy, most patients exhibit limited responses, and the underlying mechanisms are closely related to metabolic dysregulation within the tumor immune microenvironment. However, a comprehensive review of how to systematically leverage metabolic interventions to enhance immunotherapy efficacy is lacking. This review examines the competitive interactions between tumor and immune cells within essential metabolic pathways, including those involving glucose, amino acids, lipids, and nucleotides. This metabolic stress leads to the functional exhaustion of effector immune cells and activation of immunosuppressive cells, thereby promoting immune escape. Based on these mechanisms, we further summarize therapeutic strategies that target key metabolic enzymes to reshape the immune microenvironment and discuss their integration with strategies and clinical advances such as immune checkpoint blockade or CAR-T cell therapy. This review systematically integrates the core mechanisms and cutting-edge strategies at the intersection of metabolism and immunity, provides a theoretical framework and methodological reference for basic research and clinical translation in this area, and offers a theoretical basis and translational perspective for the development of synergistic metabolic–immunological therapeutic strategies.