Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades.
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http://dx.doi.org/10.3390/genes14030684 | DOI Listing |
Ann Surg
January 2025
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Objective: To investigate the clinicopathological features and long-term outcomes of cystic and solid pancreatic neuroendocrine tumors (PanNETs).
Summary Background Data: PanNETs uncommonly present as cystic lesions. Whether cystic PanNETs represent a distinct clinical entity compared to solid PanNETs is controversial.
Curr Cardiol Rev
January 2025
Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.
Cardiovascular-kidney-metabolic (CKM) syndrome is the association between obesity, diabetes, CKD (chronic kidney disease), and cardiovascular disease. GDF-15 mainly acts through the GFRAL (Glial cell line-derived neurotrophic factor Family Receptor Alpha-Like) receptor. GDF-15 and GDFRAL complex act mainly through RET co-receptors, further activating Ras and phosphatidylinositol-3-kinase (PI3K)/Akt pathways through downstream signaling.
View Article and Find Full Text PDFClin Kidney J
January 2025
Department of Medicine, Universidad Autonoma de Madrid and IIS-Fundacion Jimenez Diaz, Madrid, Spain.
Chimeric antigen receptor T (CAR-T) cell therapy, an emerging personalized immunotherapy for various haematologic malignancies, autoimmune diseases and other conditions, involves the modification of patients' T cells to express a chimeric antigen receptor that recognizes tumour or autoimmune cell antigens, allowing CAR-T cells to destroy cancerous and other target cells selectively. Despite remarkable clinical improvements in patients, multiple adverse effects have been associated with CAR-T cell therapy. Among the most recognized adverse effects are cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and tumour lysis syndrome.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100029, China.
Anthracyclines (ANTs) are widely used in cancer therapy, particularly for lymphoma, sarcoma, breast cancer, and childhood leukemia, and have become the cornerstone of chemotherapy for various malignancies. However, it is associated with fatal and dose-dependent cardiovascular complications, especially cardiotoxicity. Mitochondrial quality control mechanisms, encompassing mitophagy, mitochondrial dynamics, and mitochondrial biogenesis, maintain mitochondrial homeostasis in the cardiovascular system.
View Article and Find Full Text PDFMediastinum
November 2024
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Background: Thymoma is a rare mediastinal neoplasm originating from thymic epithelial cells, often associated with paraneoplastic syndromes. These syndromes can manifest as a range of autoimmune disorders, including myasthenia gravis, pure red cell aplasia, and aplastic anemia. Clinical trials involving the use of immune checkpoint inhibitors (ICIs) in thymoma have been complicated by a high incidence of immune-related adverse effects (irAEs).
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