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Anti-Diabetic Drug Found to Synergise Chemotherapy in Breast Cancer Cells

01 Oct 2015

Breast cancer is a major cause of cancer-related deaths among women as controlling the recurrence and metastasis (spreading) of the disease remains a major challenge. One possible explanation is that while many cancer therapies eliminate the bulk of tumour cells, they may ultimately fail because they do not eliminate cancer stem cells (CSCs) (the original cells where the cancer cells arise). CSCs are the culprit cells that are more resistant to therapies and may lead to cancer progression, recurrence, and metastasis. Indeed, the CD44+/CD24-/low breast CSCs are found in abundance in residual breast cancers after chemotherapy. These observations suggest that to be effective, cancer therapies should include drugs that target CSCs and non-CSCs to prevent the regrowth of breast cancer cells. The good news is studies have found that metformin has been reported to improve treatment efficacy to chemotherapy in diabetic breast cancer patients. Metformin is a relatively safe drug that is widely used for the treatment of Type II diabetes, obesity and polycystic ovarian syndrome (PCOS). Importantly, a number of reports have demonstrated that CD44+/CD24-/low breast cancer stem cells are resistant to chemotherapeutic drugs, but are sensitive to metformin. The mechanism as to how metformin enhances the effects of chemotherapy remains elusive. C1 In August 2015, a team led by Prof Leong Chee Onn from the International Medical University’s (IMU) Centre for Cancer and Stem Cell Research and Prof Teo Soo Hwang from Cancer Research Malaysia, revealed that metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy in both breast cancer stem cells and non-stem breast cancer cells (Apoptosis, 2015; 20: 1373-1387). This is achieved by hampering the production of ATP (energy molecules) and subsequently impairing the repair of DNA damage induced by the chemotherapeutic agents. These findings have important implications as FEC is one of standard treatment for breast cancer in the clinics. Overall, the study suggests that combination therapy with metformin and FEC may be a useful approach for treating patients with refractory breast cancers and warrant future clinical studies. Prof Leong Chee Onn is also affiliated with the School of Pharmacy, IMU. Prof Teo Soo Hwang is the Chief Executive of Cancer Research Malaysia and an Adjunct Professor at the University Malaya, Malaysia. Other members of the research team include lead authors Ms Jaslyn Soo Sian-Siu Soo and Dr Ng Char-Hong as well as co-authors Ms Tan Si Hoey, Prof Rozita Abdul Malik, Dr Teh Yew-Ching, Dr Tan Boon-Shing, Dr Ho Gwo-Fuang, Dr See Mee-Hoong, Prof Nur Aishah Mohd Taib, Dr Yip Cheng-Har, Dr Felicia Chung Fei-Lei and Ms Hii Ling-Wei. Related articles: Breast Cancer Part 1: Basic Facts Breast Cancer Part 2: Diagnosis Process Breast Cancer Part 3: Treatment Options

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