Medullary Thyroid Cancer: Molecular Drivers and Immune Cellular Milieu of the Tumour Microenvironment-Implications for Systemic Treatment. Cancers In this review, we explore the underlying molecular biology of medullary thyroid carcinoma (MTC) and its interplay with the host immune system. MTC is consistently driven by a small number of specific pathogenic variants, beyond which few additional genetic events are required for tumorigenesis. This explains the exceedingly low tumour mutational burden seen in most MTC, in contrast to other cancers. However, because of the low tumour mutational burden (TMB), there is a correspondingly low level of tumour-associated neoantigens that are presented to the host immune system. This reduces tumour visibility and vigour of the anti-tumour immune response and suggests the efficacy of immunotherapy in MTC is likely to be poor, acknowledging this inference is largely based on the extrapolation of data from other tumour types. The dominance of specific (REarranged during Transfection) pathogenic variants in MTC tumorigenesis rationalizes the observed efficacy of the targeted RET-specific tyrosine kinase inhibitors (TKIs) in comparison to multi-kinase inhibitors (MKIs). Therapeutic durability of pathway inhibitors is an ongoing research focus. It may be limited by the selection pressure TKI treatment creates, promoting survival of resistant tumour cell clones that can escape pathway inhibition through binding-site mutations, activation of alternate pathways, and modulation of the cellular and cytokine milieu of the tumour microenvironment (TME). 10.3390/cancers16132296

CAR-T cell therapy in advanced thyroid cancer: from basic to clinical. Frontiers in immunology The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field. 10.3389/fimmu.2024.1411300

The Role of Lipid Metabolism Disorders in the Development of Thyroid Cancer. International journal of molecular sciences Thyroid cancer (TC) is a neoplasm with an increasing incidence worldwide. Its etiology is complex and based on a multi-layered interplay of factors. Among these, disorders of lipid metabolism have emerged as an important area of investigation. Cancer cells are metabolically reprogrammed to promote their rapid growth, proliferation, and survival. This reprogramming is associated with significant changes at the level of lipids, mainly fatty acids (FA), as they play a critical role in maintaining cell structure, facilitating signaling pathways, and providing energy. These lipid-related changes help cancer cells meet the increased demands of continued growth and division while adapting to the tumor microenvironment. In this review, we examine lipid metabolism at different stages, including synthesis, transport, and oxidation, in the context of TC and the effects of obesity and hormones on TC development. Recent scientific efforts have revealed disturbances in lipid homeostasis that are specific to thyroid cancer, opening up potential avenues for early detection and targeted therapeutic interventions. Understanding the intricate metabolic pathways involved in FA metabolism may provide insights into potential interventions to prevent cancer progression and mitigate its effects on surrounding tissues. 10.3390/ijms25137129

Ferroptosis in thyroid cancer: Potential mechanisms, effective therapeutic targets and predictive biomarker. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Thyroid cancer is a prevalent endocrine malignancy whose global incidence has risen over the past several decades. Ferroptosis, a regulated form of cell death distinguished by the excessive buildup of iron-dependent lipid peroxidates, stands out from other programmed cell death pathways in terms of morphological and molecular characteristics. Increasing evidence suggests a close association between thyroid cancer and ferroptosis, that is, inducing ferroptosis effectively suppresses the proliferation of thyroid cancer cells and impede tumor advancement. Therefore, ferroptosis represents a promising therapeutic target for the clinical management of thyroid cancer in clinical settings. Alterations in ferroptosis-related genes hold potential for prognostic prediction in thyroid cancer. This review summarizes current studies on the role of ferroptosis in thyroid cancer, elucidating its mechanisms, therapeutic targets, and predictive biomarkers. The findings underscore the significance of ferroptosis in thyroid cancer and offer valuable insights into the development of innovative treatment strategies and accurate predictors for the thyroid cancer. 10.1016/j.biopha.2024.116971

The treatment of advanced melanoma: Current approaches and new challenges. Critical reviews in oncology/hematology In recent years, advances in melanoma treatment have renewed patient hope. This comprehensive review emphasizes the evolving treatment landscape, particularly highlighting first-line strategies and the interplay between immune-checkpoint inhibitors (ICIs) and targeted therapies. Ipilimumab plus nivolumab has achieved the best median overall survival, exceeding 70 months. However, the introduction of new ICIs, like relatlimab, has added complexity to first-line therapy decisions. Our aim is to guide clinicians in making personalized treatment decisions. Various features, including brain metastases, PD-L1 expression, BRAF mutation, performance status, and prior adjuvant therapy, significantly impact the direction of advanced melanoma treatment. We also provide the latest insights into the treatment of rare melanoma subtypes, such as uveal melanoma, where tebentafusp has shown promising improvements in overall survival for metastatic uveal melanoma patients. This review provides invaluable insights for clinicians, enabling informed treatment choices and deepening our understanding of the multifaceted challenges associated with advanced melanoma management. 10.1016/j.critrevonc.2024.104276