Total budget: 48.000.000 HUF

Project manager: Dr. Edward Eric Schmidt

Duration:

from 1st December 2022. to 30th November 2026.

 

Summary:

Whereas survival rates for many common cancers have increased dramatically over the past several decades, liver cancer and several others remain nearly untreatable. Cancer researchers seeking new approaches to treating refractory tumors have recently turned attention to the predicted oxidative stress sensitivity of cancer cells. Thus, due to the metabolic rewiring of cancer cells, they tend to generate more oxidants themselves, and get exposed to more oxidants from their environment, than do other cells. However, attempts to drug the canonical antioxidant systems in cancers have, as yet, enjoyed little success. The proposing researchers have many years of experience developing and studying genetically engineered mice (GEMs) specialized for understanding the antioxidant systems in normal livers or in liver cancer. These studies have revealed backup systems that can support the cells when the normal antioxidant systems are blocked, and they have revealed that the regulator Nrf2 plays a key role in controlling this process. Nrf2 is already known as a dominant driver of cancer malignancy; however the first report of a specific Nrf2 inhibitor only appeared in late 2021. In the proposed project, we will instead identify other components of the backup antioxidant systems, many of which are likely controlled by Nrf2, that might play critical roles in protecting cancer cells and might be more druggable than Nrf2. We can then test combination therapies that coincidentally block both the normal redox systems and the backup systems together as potential new treatments for liver cancer and possibly other currently untreatable cancers.