08 Dec Older Diabetes Drug Metformin May Resensitize Tumors to Chemotherapy

MedicalResearch.com Interview with:

Dr. Arnason

Terra G Arnason, MD PhD, Associate Professor,
Division of Endocrinology,
Department of Medicine
University of Saskatchewan
Saskatoon, SK, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Response: Metformin has been used worldwide for decades to treat Type diabetes.

Metformin is a cheap non-toxic compound that was originally plant derived. In the past decade a number of meta-analyses have demonstrated that Type 2 individuals taking
metformin have a reduced risk of developing many different cancers and do better
longterm. The molecular events facilitating metformin’s activity remain obscure and
it is unknown whether metformin can help cancer patients avoid the development of
drug resistant cancers years after successful treatment.

In our study we asked whether metformin can not only restore sensitivity of multiple drug resistant tumors to chemotherapy once again, but whether metformin can prevent the development of multiple drug resistance in the “rst place. We demonstrate that metformin can sensitize drug resistant cells to chemotherapy once again, which supports recent
studies, but we also show for the “first time that Metformin can prevent the
progression of cancer cells towards drug resistance using cell culture experiments.

MedicalResearch.com: What should readers take away from your report?

Response: In this report we conducted a timecourse assessment to determine the point cancer cells become drug resistant following our protocol that generates drug resistant cells. We show that after only 24-48 hours of exposure to chemotherapy (Doxorubicin), protein markers of drug resistance, such MDR-1 (multiple drug resistance-1) and BCRP (breast cancer resistance protein), are expressed. Importantly, these cells are still drug sensitive; drug resistance does not occur until day 10 of the protocol. This indicates, if this work can be translated to animal models, that there is a chance that multiple drug resistant tumors can be detected prior to clinical presentation, and avoid futile therapy.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Our current and future work extending from this study will involve molecular analyses of why drug resistance develops, and will require moving into animal models.

We are currently recruiting companion canines that present to the veterinary clinic at the Western College of Veterinary Medicine in Saskatoon, with spontaneous lymphoma. Canine lymphoma is very similar to the variety observed in humans, is treated with the same chemotherapy regime, and frequently develops into a multiple drug resistant form.

Currently in our study, when a canine develops drug resistance, confirmed by the expression of multiple drug resistance protein markers (MDR-1 and BCRP), they receive Metformin in combination with chemotherapy. In all case (5), MDR-1 and BCRP protein markers reduce within a week, and in one of these cases, in a dog that had failed all previous treatments, remission occurred, which lasted 2 months. We obtained RNA samples from the canine prior to treatment, following treatment and remission, and then after relapse. We identified a set of RNAs that were elevated in drug resistant cells, compared to normal control cells, that were reduced upon remission and elevated once again when the dog relapsed. This set of genes identifies a new potential mechanism that promotes the development of aggressive cancer.

MedicalResearch.com: Is there anything else you would like to add?

Response: We would like to thank the Canadian Cancer Society for supporting and funding this work, the University of Saskatchewan and the College of Medicine for providing the resources for conduction this study, and the dog owners and veterinarians within Western College of Veterinary Medicine for their collaboration on our future studies. Lastly, we would like to thank PLoS ONE for publishing our work. 

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Last Updated on December 8, 2017 by Marie Benz MD FAAD