February 11 2019. A report published on February 6, 2019 in Nature Communications reveals a role for the diabetes drug metformin in combination with the BCL-2 protein inhibitor venetoclax in the treatment of breast cancer.
The combination was designed to take advantage of an increased sensitivity of breast cancer cells to undergo apoptosis (a type of programmed cell death) associated with the presence of a cancer-initiating gene known as MYC, which is overexpressed in more than 40% of breast cancers. Metformin increases ventoclax’s ability to induce apoptosis in cancer cells.
"This drug combo exploits specific metabolic vulnerabilities that high levels of MYC create in tumor cells,” explained lead researcher Juha Klefström of the University of Helsinki. “Metformin and venetoclax, when given together, killed breast tumor cells in culture and blocked tumor growth in breast cancer animal models. Furthermore, the drugs efficiently killed authentic breast cancer tissue donated by breast cancer patients."
Although the metformin plus venetoclax combination was effective in mice with implanted breast tumors, withdrawal of the drugs led to tumor regrowth. The addition of a PD-1-targeted immunotherapy to the two-drug regimen after the removal of the primary tumor prolonged the activity of killer lymphocytes, even after drug withdrawal. "With this combination the survival of mice carrying implanted tumors was extended dramatically in comparison to mice that were treated with only single or double combinations,” Dr Klefström stated.
"We finally have a drug combination that efficiently exploits MYC's apoptotic function and most importantly, these drugs can be tested in the clinic in real patients," he concluded.
"This is a great example of how scientists in academia, leveraging highly specialized tumor models and applying their unique insights, can contribute to the discovery of potential new treatments for people with cancer,” added co-senior author Joel Leverson, PhD.
Source: https://www.lifeexte...ge-01#Metformin
Edited by Engadin, 15 February 2019 - 04:04 PM.
