Targeted Protein Degradation (TPD) offers a solution, eliminating disease-related proteins and overcoming challenges associated with unintended toxicity and lack of precision. PROTACs (Proteolysis Targeting Chimeras) represent an innovative strategy for the specific degradation of tar-get proteins through the UPS (Ubiquitin-Proteasome System). In comparison to conventional protein inhibitor medications, PROTAC offers advantages in terms of efficacy, selectivity, and the ability to overcome drug resistance in cancer treatment, contributing novel perspectives to the field of anti-cancer drug discovery. Proteins play vital roles in an organism's health, and misfolded contributes to diseases like neurodegenerative disorders and cancer. Cells maintain protein balance through quality control systems, primarily the UPS and autophagy. Protac, a Targeted Protein Degradation (TPD) strategy, utilizes UPS, employing small molecules to induce targeted protein degradation. PROTAC exhibits promise in preclinical studies and clinical trials for diverse cancers. Notable examples in-clude breast cancer, where PROTAC targets CDK4/6 (cyclin-dependent kinase) and Estrogen Recep-tors (ER), prostate cancer, addressing Androgen Receptor (AR) degradation, hematologic malignan-cies, focusing on AURORA-A and CDKs, and NSCLC (Non-Small-Cell Lung Cancer), targeting Estimated Glomerular Filtration Rate (EGFR), and KRAS. Despite their potential, PROTAC faces challenges, including compensatory protein expression in response to targeted therapies. This com-prehensive review explores recent advancements in PROTAC and related technologies, emphasizing the mechanisms and structures of PROTAC and their applications in proteins targeting cancer.
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http://dx.doi.org/10.2174/0115701638324854250218053353 | DOI Listing |
FASEB J
March 2025
Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Neuron-derived clone 77 (Nur77), a member of the orphan nuclear receptor family, is expressed and activated rapidly in response to diverse physiological and pathological stimuli. It exerts complex biological functions, including roles in the nervous system, genome integrity, cell differentiation, homeostasis, oxidative stress, autophagy, aging, and infection. Recent studies suggest that Nur77 agonists alleviate symptoms of neurodegenerative diseases, highlighting its potential as a therapeutic target in such conditions.
View Article and Find Full Text PDFBone Joint Res
March 2025
Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China.
Aims: Osteoarthritis (OA) is a widespread chronic degenerative joint disease with an increasing global impact. The pathogenesis of OA involves complex interactions between genetic and environmental factors. Despite this, the specific genetic mechanisms underlying OA remain only partially understood, hindering the development of targeted therapeutic strategies.
View Article and Find Full Text PDFFASEB J
March 2025
Cancer Center, The First Affiliated Hospital of Jilin University, Changchun, Jilin, China.
Breast cancer (BC) is one of the most common malignant tumors among women, accounting for 24.5% of all cancer cases and leading to 15.5% of cancer-related mortality.
View Article and Find Full Text PDFOMICS
March 2025
Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India.
Intracellular calcium signaling is a cornerstone in cell biology and a key molecular target for human health and disease. Calcium/calmodulin dependent protein kinase kinases, CAMKK1 and CAMKK2 are serine/threonine kinases that contribute to the regulation of intracellular calcium signals in response to diverse stimuli. CAMKK1 generally has stable dynamics, whereas CAMKK2 dysregulation triggers oncogenicity and neurological disorders.
View Article and Find Full Text PDFCancer Med
March 2025
Universidad Autónoma del Estado de Morelos, Facultad de Medicina, Cuernavaca, Morelos, Mexico.
Introduction: Osteosarcoma, a highly aggressive bone cancer primarily affecting children and young adults, remains a significant challenge in clinical oncology. Metastasis stands as the primary cause of mortality in osteosarcoma patients. However, the mechanisms driving this process remain incompletely understood.
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