The tumor immune microenvironment (TIME) represents a complex battlefield where metabolic competition and immune evasion mechanisms converge to drive cancer progression. Amino acids, with their multifaceted biological roles, have emerged as pivotal regulators of tumor cell proliferation and immune cell functionality. The sensing mechanisms by which amino acids within the tumor microenvironment influence cellular growth, survival, and immune function are systematically explored in this review; the latest advances in understanding amino acid metabolism in tumor biology are also reviewed. In addition, the multifaceted roles of key amino acids in shaping the TIME with particular emphasis on tumor immunity and malignant growth were investigated. Finally, emerging therapeutic strategies targeting amino acid metabolism to reprogram the TIME are discussed, highlighting promising approaches, such as CAR-T cell therapy and engineered bacterial interventions. Through this comprehensive analysis, critical insights into future research directions and potential clinical translation of amino acid-targeted interventions are provided.

Prostate cancer (PCa) is a leading cause of cancer-related mortality among men. Radiotherapy is the cornerstone of PCa treatment. However, a major limitation of radiotherapy is the development of resistance, which compromises treatment efficacy. Reactive oxygen species (ROS), which are generated by radiation, have a dual role in PCa by inducing DNA damage and apoptosis, while also promoting tumor progression and radioresistance. Elevated ROS levels enhance metabolic reprogramming, activate oncogenic pathways, and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition (EMT). Key molecular mechanisms, including the Nrf2/Keap1 signaling axis, Bcl-2 mutations, and Speckle-type POZ protein alterations, contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity. Additionally, the interplay between hypoxia, androgen receptor variants (AR-Vs), and ferroptosis regulators further influence radiotherapy outcomes. Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis that is driven primarily by oncogenic KRAS mutations present in > 90% of cases. KRAS mutations, particularly the G12D mutation which dominates in PDAC, fuel tumor initiation, progression, and immune evasion, thereby contributing to therapy resistance. Nevertheless, KRAS has long been considered “undruggable” due to its structure. Recent advances have spurred transformative progress in direct KRAS inhibition. While FDA-approved mutation-specific and pan-KRAS inhibitors show limited efficacy in PDAC, emerging agents (MRTX1133 and RMC-9805) have demonstrated preclinical promise. However, resistance remains a critical hurdle and is driven by pathway reactivation, secondary mutations, and metabolic adaptations. Alternative strategies targeting upstream regulators (SHP2 and SOS1) aim to block KRAS activation and associated resistance mechanisms. Preclinical studies have also highlighted synergistic benefits of combining KRAS inhibitors with MEK, PI3K, or CDK4/6 inhibitors, which are now undergoing clinical evaluation. Immunotherapies, including KRAS-targeted vaccines and adoptive T-cell therapies, have further expanded the therapeutic landscape of enhancing KRAS-targeted therapies in PDAC. The molecular basis of KRAS-driven PDAC, current inhibitors, resistance mechanisms, and innovative strategies are discussed herein to address treatment barriers. Opportunities to improve clinical outcomes are underscored in this challenging malignancy by integrating insights from preclinical and clinical research.

Breast cancer (BC) has the highest prevalence among cancers specific to women, and its incidence rates are increasing in many countries. Subtypes of BC, including HER2-positive or triple-negative BC, exhibit differing treatment responses; consequently, demand for personalized therapy is increasing, and relevant precision medicine strategies are under development. Aerobic glycolysis in cancer cells can lead to excessive lactate production, which in turn promotes lactylation and influences tumor cell behavior. Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors. Because lactate and lactylation are important in cancer, further investigation of the mechanisms underlying lactate metabolism and lactylation, and the development of therapeutic strategies targeting these processes, are topics of increasing interest. This review describes current research on lactate metabolism and lactylation in BC, thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.