Stacy Blain, co-founder and Chief Scientific Officer of Concarlo Therapeutics, discusses drug resistance in cancer and the development of therapies to target drug-resistant breast cancer. The chapter also explores the role of P27 protein in cancer biology and the challenges faced by women in the biotech industry. The speaker provides insights into the company's funding journey and upcoming research and clinical trials.
Targeting the proteins CdK2, CdK4, and CdK6 that play a critical role in cell proliferation can help overcome drug resistance in cancer.
Drugging the protein P27, which serves as the master regulator of CdK2, CdK4, and CdK6, can lead to therapies with fewer off-target effects and greater specificity.
Deep dives
Development of Drug Resistance in Cancer and the Unmet Need in Breast Cancer
Despite advances in cancer treatment and the development of precision oncology drugs, drug resistance remains a significant problem. In the United States alone, breast cancer claims the lives of 40,000 people each year, highlighting the large unmet need in this area. Tumors are highly evolving entities that can evolve away from current precision oncology therapies. New therapies that specifically target resistance mechanisms are necessary to address this issue. Concala Therapeutics is focused on developing therapies for drug-resistant breast cancer and other tumor types, particularly targeting the proteins CdK2, CdK4, and CdK6 that play a critical role in cell proliferation. By targeting these proteins, Concala aims to shut down the bottom of the oncogenic funnel and overcome drug resistance in cancer.
The Role of P27 in Cell Cycle Regulation and Its Potential as a Therapeutic Target
P27 is a protein that serves as the master regulator of CdK2, CdK4, and CdK6, the proteins responsible for cell cycle regulation. Normally, P27 receives signals from the cell surface and cytoplasm to activate or inhibit these kinases, controlling the decision of cell division. Concala Therapeutics has chosen to target P27 as a therapeutic approach because specifically targeting CdK2, CdK4, and CdK6 has proven challenging due to the similarity of these proteins to other CDK family members. By drugging P27 and getting it to do its job of blocking the kinases, Concala aims to develop therapies with fewer off-target effects and greater specificity.
Concala's Lead Program and Future Directions
Concala's lead program is based on a natural inhibitor of P27 called ALT. By blocking the keyhole of P27, ALT keeps the protein locked and prevents the activation of CdK2, CdK4, and CdK6. This peptide-based lead asset is delivered via liposomes, which protect the therapeutic payload and facilitate delivery to tumor cells. Concala has conducted preclinical studies demonstrating efficacy and preliminary toxicity experiments. The company is preparing for IND-enabling studies to demonstrate the safety of its therapy and aims to enter clinical trials in approximately 18 months. Furthermore, while initially focusing on breast cancer, Concala recognizes the potential to use its approach in other tumor types and is developing secondary assets, including smaller molecules and alternative delivery methods, to address different cancer challenges.
The advent of targeted therapies has contributed to notable progress in the fight against cancer, but the ability of cancers to develop resistance to these precision medicines continues to leave patients in need of new approaches. Concarlo Therapeutics is developing therapies that target a critical driver of cell proliferation that is reactivated once a cancer grows resistant to certain targeted therapies. We spoke to Stacy Blain, co-founder and chief scientific officer of Concarlo, about the development of drug resistance in cancer, the company’s initial focus on breast cancer, and her own journey from academia to biopharma.
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