Targeting the Chaperone-Mediated Folding of CDK4 in Kidney Cancer
Abstract
Large molecular machines in cells control the fate of the biomolecules that carry out specific tasks required for survival, development, and growth. The activities of these machines are highly dysregulated in pathogenic conditions, such as cancer. While responsible for processes that ultimately lead to disease, these molecular machines offer attractive therapeutic targets for the development of new drugs. The focus of this FY21 KCRP project is the development of novel therapeutic strategies for the treatment of kidney cancer, based on a novel mechanistic-based approach. In particular, the project will start from an understanding of the biological and biophysical mechanisms of integration between proteins responsible for kidney cancer development and the cell machinery that oversees their correct functioning. On this basis, new molecules will be designed and experimentally tested to act as wedges that block the functioning of the machinery underlying cancer-related pathogenic mechanisms. Specifically, these new concepts will be applied to block the function of proteins of key importance for kidney cancer. If successful, this project will deliver new knowledge, methods, and drug design approaches to target kidney cancer with a novel mechanistic approach. In the short term, the project will provide new chemical tools to investigate cancer mechanisms and begin a process of drug development towards actionable drugs. The results may benefit patients by delivering new treatments that overcome the toxicity and off-target and limited effects of currently used U.S. Food and Drug Administration-approved drugs for kidney cancer. Moreover, being based on general concepts, the methodology outlined here can aptly be extended to targeting other types of cancers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210158
Entities
People
- Giorgio L Colombo
Organizations
- United States Army
- University of Pavia