In recent years, the mechanisms of abnormal metabolite accumulation in tumor development have become an emerging research field. Cells within the tumor microenvironment (TME) sustain tumor proliferation via metaboalic reprogramming. Such metabolic remodeling triggers aberrant oncometabolite accumulation, which drives tumor progression, distant metastasis and therapeutic resistance through the modulation of tumor cell proliferation, angiogenesis and immune evasion. Notably, fumarate and itaconate, originating from different subcellular localizations, modulate protein function primarily covalent or non-covalent interactions. Functionally, the modified target proteins can be roughly divided into four categories that drive tumor progression: key metabolic enzymes, epigenetic regulators, immune-related molecules and resistance-associated proteins, which respectively modulate metabolic rewiring, epigenetic reprogramming, the immunosuppressive microenvironment and therapeutic resistance. Herein, we systematically summarize the oncogenic mechanisms of these two oncometabolites, propose viable strategies to address technical hurdles in studying non-enzymatic protein modifications and offer new directions for the clinical treatment of tumors through targeted inhibition of fumarate and itaconate.
Yi-Dan Fan, Han-Qiu Zhang, Jinkun Qin et al.· Seminars in Oncology· 0 citations
ABSTRACT
Breast cancer remains the most common cancer among women worldwide, characterized by significant molecular heterogeneity. Advances in targeted therapy and immunotherapy have transformed treatment approaches, offering promising new options for patients. Targeted therapies are designed to inhibit the key pathways that drive tumor growth and survival. The cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, phosphatidylinositol-3 kinase (PI3K) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and other treatments have significantly advanced treatment, delaying progression and extending survival for some subtypes of breast cancer. Nevertheless, targeted therapeutic agents have not yet demonstrated significant clinical efficacy in the treatment of triple-negative breast cancer (TNBC). Meanwhile, immunotherapy has emerged as a complementary approach. Immune checkpoint inhibitors (ICIs) have demonstrated notable efficacy in subsets of TNBC and are under exploration in other breast cancer subtypes, including hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) and HER2-positive disease. Furthermore, innovative strategies such as anticancer vaccines and adoptive T-cell therapy offer potential for prolonged immune engagement and tumor eradication. This review provides an overview of current progress in targeted therapies and immunotherapy for breast cancer, highlighting their mechanisms, clinical utility, and challenges. By integrating knowledge from recent advancements, this review seeks to guide future research and clinical practice toward improved and personalized care for breast cancer patients.
Song Wu, Pangzhou Chen, Wen Zhou et al.· Chinese Medical Journal· 0 citations
This study comprehensively maps the coevolution of malignant thyrocyte plasticity and the immunosuppressive metastatic niche in thyroid cancer and provides a robust molecular rationale for developing next-generation immunotherapeutic strategies tailored to thyroid cancer.
Shu-hang Xu, Yaorong Su, Senmin Zhang et al.· Oncoimmunology· 0 citations
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