Scientists led by Dr. Saïd Sebti at VCU Massey Cancer Center have developed a groundbreaking therapy targeting the KRAS protein found in deadly cancers like pancreatic, lung, and colon tumors. Their study, published in Cancer Research Communications, highlights a potential inhibitor for KRAS G12D, a subset of the cancer-driving KRAS gene.
The research involved collaboration among scientists from renowned cancer centers, including the Moffitt Cancer Center, Montefiore Einstein Comprehensive Cancer Center, University of Florida Health Cancer Center, and the Cancer Center at Illinois.
Sebti, the associate director for basic research and the Lacy Family Chair in Cancer Research at Massey said, “This discovery is a major step forward in our battle against some of the most aggressive forms of cancer. Our collaborative effort signifies a leap forward in the development of targeted therapies against KRAS-driven cancers such as pancreatic cancer.”
In this study, Sebti’s team partnered with the Cancer Center at Illinois to find drugs that block KRAS and stop it from causing cancer. They discovered a powerful drug, KRAS Binder-456 (KRB-456), which significantly inhibited the growth of pancreatic cancer tumors in mice that were resistant to traditional treatments. Further testing will explore using KRB-456 alongside standard cancer treatments, potentially enhancing its effectiveness or informing the development of a more potent drug against KRAS G12D-driven tumors.
Sebti said, “For every researcher in the field of oncology, the ultimate aspiration is to make a tangible difference in the lives of cancer patients. As we progress toward this goal, the excitement mounts, knowing that our work could directly impact those battling this devastating disease.KRAS used to be called the ‘undruggable target.’ But we and others have now shown that it is druggable. We hope our continued work will lead to the development of effective drugs for KRAS G12D-driven cancers.”
In conclusion, the groundbreaking discovery of the promising anticancer drug targeting the KRAS protein represents a significant advancement in cancer research. The identified drug, KRAS Binder-456 (KRB-456), shows potential in inhibiting the growth of tumors associated with mutant KRAS genes, offering hope for more effective treatments against deadly cancers like pancreatic, lung, and colon tumors.
This discovery marks a crucial step forward in addressing the challenges posed by KRAS-driven cancers, opening new possibilities for innovative therapeutic interventions.
Journal reference:
- Aslamuzzaman Kazi, Alok Ranjan, et al., Discovery of KRB-456, a KRAS G12D switch-I/II allosteric pocket binder that inhibits the growth of pancreatic cancer patient-derived tumors. Cancer Research Communications. DOI: 10.1158/2767-9764.CRC-23-0222.