It is a popular diabetes medication but two new clinical studies were presented at the annual meeting of the American Association for Cancer Research. It was found that metformin may slow the rate of prostate cancer growth in certain patients, and in prolonging life for early-stage pancreatic cancer patients. The drug might have an effect against liver or oral tumors, as well as certain forms of melanoma and this study was done either in the lab or in animals. Metformin is also found to be effective against colon and breast cancer.
Anti-cancer mechanism of metformin is still unclear. It remains to be seen who would benefit the most from metformin. The most appropriate patients may be those with diabetes, those who are at risk for the disease or those whose tumors are sensitive to metformin.
In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake (by phosphorylating GLUT-4 enhancer factor), increases fatty acid oxidation and decreases absorption of glucose from the gastrointestinal tract. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors.
We know that cancer cell is abnormal cell which shows uncontrolled growth. Hence it needs more energy by glucose utilization. May be cancer cells are more sensitive to insulin. When healthy cells become less sensitive to insulin, cancer cell is more benefited by those circulating insulin. Moreover cancer cells get more glucose for utilization when glucose is not properly utilized by healthy cells. Metformin increases peripheral glucose utilization and insulin sensitivity in healthy cells and thus creates an energy crisis of cancer cells due to less availability of circulating insulin and glucose.
Aspirin at 75 mg is prophylactically administered for heart attacts. At higher doses it is a popular analgesic, antpyratic and NSAID. Recent research shows that it may play a role in cancer prevention. It slows down the spread of cancer and metastasis. It is found to be effective in colon cancer.
How does it work? The answer is not yet been confirmed. At low dose aspirin inhibits platelets which promote clotting and also help cancer cells spread. Anti-inflammatory effect of cancer may slow down the swelling of cancer leison. It also prevent lymphatic metastasis by inhibiting VEGF-D-driven metastasis by interfering with the prostaglandin pathway and blocking lymphatic vessel dilation.
There is also a evidence that aspirin may prevent skin cancer. Patients taking aspirin or other NSAIDs had a 15% decreased risk for developing squamous cell carcinoma and a 13% lower risk of malignant melanoma. NSAIDs did cut the risk of basal cell carcinomas developing on certain parts of the body other than the head and neck but NSAIDs can’t lower the overall risk of basal cell carcinoma – the most common and least aggressive type of skin cancer.
There is an interesting association of beta blockers with several cancer like nonsmall-cell lung cancer (NSCLC), breast cancer and malignant melanoma. Beta-blocker use is associated with improved distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) in NSCLC patients. Beta adrenergic receptor mediates tumor cell migration which is directly stimulated by noradrenaline. Beta adrenergic pathway can induce proliferation, invasion and migration of tumor cells which can lead to development of tumor in distant parts of the body. This pathway leads to Src activation via a unique protein kinase A (PKA)-mediated mechanism, which is critical to the regulation of cellular activity and cancer metastasis. Src (pronounced “sarc,” short for sarcoma) is a proto-oncogene – a normal gene that can become an oncogene due to increased expression – involved in the regulation of cell growth and division. When the adrenergic receptors on cancer cells are activated, they set into motion a chain of events that leads to formation of new blood vessels that feed tumor growth – a process known as angiogenesis. New blood vessel formation allows tumors to grow and spread more rapidly. Beta blockers inhibit this pathway and in doing so it can prevent the distant spread of tumor cells.
If we want to treat any cancer patient with beta blockers, we may need to know that is there any significant increase in biosynthesis of noradrenaline or any increased affinity of adrenergic receptor for noradrenaline in that particular patient body. It is necessary because adrenaline or noradrenaline is also beneficial for the body. May be there is any imbalance in the biosynthesis of this two in cancer patients. Further study is needed to establish anticancer effect of beta blocker.
- Metformin Protects against Liver, Oral, Prostate and Pancreatic Cancers (nextbigfuture.com)
- Metformin May Protect Against Lung Cancer (prweb.com)
- Diabetes drugs tied to pancreatic cancer risk (msnbc.msn.com)
- Could a NOSH-Aspirin-a-Day Keep Cancer Away? (InnovationToronto.com)
- Role of Antidiabetics in Pancreatic Cancer Risk Unclear (livingstrongandhappy.blogspot.com)
- Metformin: Diabetes Drug Does Double-Time As Cancer Drug (inquisitr.com)
- New Clues to Link Between Fatty Diet, Colon Cancer (nlm.nih.gov)
- Aspirin may halt cancer spread (independent.co.uk)
- More Evidence Shows That Daily Aspirin Might Combat Cancer (news.health.com)
- Lung Cancer Patients Live Longer If They Use Beta-Blockers While Receiving Radiotherapy (medicalnewstoday.com)