Proteolysis targeting chimeria (PROTAC) degrades target proteins by utilizing the ubiquitin-proteasome pathway, subverting the concept of traditional small molecule inhibitors. Among the common mutation targets of non-small cell lung cancer (NSCLC), PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK ) and other proteins in preclinical studies. PROTAC drugs with their unique event-driven advantages, are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets, thereby providing a new strategy for the treatment of NSCLC. .
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http://dx.doi.org/10.3779/j.issn.1009-3419.2022.102.19 | DOI Listing |
J Gastrointest Cancer
January 2025
Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Recent advances in targeted therapies have opened new avenues for intervention in PDAC, focusing on key genetic and molecular pathways that drive tumor progression.
Methods: In this review, we provide an overview on advances in novel targeted therapies in pancreatic adenocarcinoma.
Ther Adv Med Oncol
January 2025
Division of New Drugs and Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, Milan 20141, Italy.
Antibody-drug conjugates (ADCs) have emerged as a transformative approach in cancer therapy by enhancing tumor targeting and minimizing systemic toxicity compared to traditional chemotherapy. Initially developed with chemotherapy agents as payloads, ADCs have now incorporated alternative payloads, such as immune-stimulating agents, natural toxins, and radionuclides, to improve therapeutic efficacy and specificity. A significant advancement in ADC technology is the integration of Proteolysis Targeting Chimeras (PROTACs), which enable the precise degradation of cellular targets involved in tumorigenesis.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Targeted Protein Degradation (TPD) represented by Proteolysis-Targeting Chimeras (PROTAC) is the frontier field in the research and development of antitumor therapy, in which oral drug HP518 Receives FDA Proceed Authorization for its IND Application for Prostate Cancer Treatment. Recently, molecular glue, functioning via degradation of the target protein is emerging as a promising modality for the development of therapeutic agents, while exhibits greater advantages over PROTAC, including improved efficiency, resistance-free properties, and the capacity to selectively target "undruggable" proteins. This marks a revolutionary advancement in the landscape of small molecule drugs.
View Article and Find Full Text PDFBioorg Chem
December 2024
Jiangsu Key Laboratory of Drug Design & Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:
Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostate, bladder, and chronic myeloid leukemia. Despite significant progress in the development of potent and selective FGFR inhibitors, the long-term efficacy of these drugs in cancer therapy has been hampered by the rapid onset of acquired resistance. Therefore, more drug discovery strategies are needed to promote the development of FGFR-targeted drugs.
View Article and Find Full Text PDFCell Chem Biol
December 2024
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria. Electronic address:
Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. This approach allows scope for targeting "undruggable" proteins, and several PROTACs have reached the stage of clinical candidates. However, the roles of cellular transmembrane transporters in PROTAC uptake and efflux remain underexplored.
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