Available Technology
Metformin selectively targets cancer stem cells
Technology:
Therapeutic drug
Markets Addressed
The Struhl lab demonstrated that metformin selectively targets and kills chemotherapy-resistant CSCs. The combination of metformin with existing chemotherapeutic drugs, which attack non-stem cancer cells, was shown to have a dramatic effect on reducing tumor mass and prolonging tumor remission.
A number of markers for CSCs have recently been identified, including CD133 and CD44. Several studies have shown that different types of tumors express these markers to varying degrees. Whereas some tumors contain few cells that express these markers (e.g., some hematological cancers, pancreatic and liver carcinomas), many solid tumors express high levels of the CSC markers (e.g., up to 38% of cells in breast, lung, colorectal and brain tumors).
This technology can be used to develop a novel orally-available therapy that combines metformin with a chemotherapeutic drug in a single pill. Many currently marketed orally-available chemotherapeutic drugs are indicated for the first- and second-line treatment of solid tumors including breast, lung, colorectal, prostate, and renal cell carcinomas. Since many of these solid tumors have also been found to express high levels of CSC markers, this technology may offer great promise to develop a novel combination therapy for more complete treatment of solid tumors.
Innovations and Advantages
Chemotherapeutic treatments for cancer can effectively reduce tumor mass, but the disease often relapses. To explain this phenomenon, the cancer stem cell (CSC) hypothesis suggests that tumors contain a small number of tumor-forming, self-renewing, CSCs within a population of non-tumor-forming cancer cells. Unlike most cells within the tumor, CSCs are resistant to well-defined chemotherapy, and after treatment they can regenerate all the cell types in the tumor through their stem cell-like behavior. For this reason, drugs that selectively target CSCs offer great promise for more complete cancer treatment, although none are known at present.
Epidemiologic studies indicate that diabetes is correlated with increased risk of breast and other cancers. The Struhl laboratory recently defined a transcriptional signature and drug sensitivity profile of cellular transformation linking multiple types of cancer with diabetes and other metabolic diseases. Metformin is extensively used for the treatment of diabetes, obesity, and polycystic ovarian syndrome. Diabetics treated with metformin have reduced cancer risk, although it is unclear whether metformin affects cancer directly or indirectly by inhibiting the diabetic state. Metformin has also been shown to inhibit the growth of breast cancer cell lines and inhibit tumor growth of xenografts in a triple-negative breast cancer cell line.
The Struhl laboratory demonstrated that low doses of metformin inhibit cellular transformation and selectively kill CSCs in multiple cell lines, including lung, prostate and four genetically different types of breast cancer. The combination of metformin with several different, well-defined chemotherapeutic drugs effectively kills both CSCs and non-stem cancer cells in culture. In vivo data in xenograft solid tumor models shows that these combination therapies reduce tumor mass and prolong remission much more effectively than either drug alone. Furthermore, mice remain tumor-free for at least two months after ending the therapy. Their results provide support for the CSC hypothesis, and a rationale for combining metformin with chemotherapeutic drugs to improve the treatment of breast and other cancers.
Additional Information
Intellectual Property Status: Patent(s) pending
This technology is available for worldwide, exclusive licensing.
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Inventor(s):
Hirsch, Heather
Iliopoulos, Dimitrios
Struhl, Kevin
Categories:
For further information, please contact:
Grant Zimmermann, Director of Business Development
(617) 495-3067
Reference Harvard Case #3564