- Breast cancer is the most common cancer in women worldwide.
- 1 in 5 patients suffers from HER2 positive breast cancer, an aggressive form which is more resistant to treatment.
- Fasnall, a new compound has been found to show anti-proliferative activity against HER2 positive breast cancer cells.
- This discovery may open new doors in breast cancer research, and treatment of other cancers and HIV as well.
Of the various risk factors associated with breast cancer, genetics is an important factor in determining cancer predisposition, progression and prognosis. In around 20% of the cases of breast cancer, tumor cells express a gene mutation that produces an excess of a protein known as HER2 (Human Epidermal Growth Factor Receptor 2) protein. This protein enhances the proliferation of cancer cells and HER2 positive breast cancer, therefore, tends to be more aggressive and less sensitive to hormone therapy.
‘Fasnall, a unique compound with the ability to disrupt tumor growth, may be the new breakthrough in the treatment of aggressive breast cancer.’
At the end of the study, it was observed that the mice injected with Fasnall survived for an average of 63 days, which was more than double the survival period of mice in the control group, which was not administered Fasnall. Moreover, the tumor size reduced to two-thirds the size of those in the control group after treatment for three weeks.
When Fasnall was used along with carboplatin, a chemotherapy drug used in cancer treatment, the shrinkage of the tumor and survival period were more than that seen when either was used alone.
The efficacy of Fasnall is attributed to its property of inhibiting the action of Fatty Acid Synthase enzyme (FASN).
Role of Fatty Acid Synthase in Cancer Cell ProliferationFatty acid synthase (FASN) is a multifunctional enzyme that mediates the synthesis of palmitic acid. Normal cells of the human body do not require FASN as they get their fat from extracellular matrix. Cancer cells, on the other hand, require large quantities of lipids to support the various processes needed for the rapid proliferation and growth of the cancer. Cancers of various organs like breast, prostate, colon, and pancreas have been noted to overexpress FASN. Inhibition of FASN disrupts the membrane structure of tumor cells and mechanisms involved in cell growth, signaling and proliferation.
Thus, inhibition of FASN is a promising therapeutic strategy in cancer, where fast growing cells requiring excess fats are selectively targeted. Since FASN plays a role in HIV, such medications may also be useful in the treatment of HIV.
FASN Inhibitory Action of FasnallThe team of scientists selected Fasnall from 3400 candidate molecules based on the ability of the molecule to inhibit fatty acid synthase in pig mammary glands without causing much harm to normal cells. Fasnall demonstrated the ability to inhibit the enzyme with the use of a small quantity, thereby lowering the risk of its own toxicity.
"Fasnall inhibits the activity of this enzyme to make palmitic acid, a molecule important for many cellular processes", said Jesse Kweik, an Associate Professor of Microbiology and Microbial Infection and Immunity who led the study along with Duke University's Timothy Haystead, a Cancer biologist.
Since FASN is primarily required by tumor cells, targeting it, results in disruption of the cancer cells while sparing the normal body cells which are not dependent on FASN. This is a major advantage while looking for a chemotherapeutic drug with least side effects on the normal cells.
Disruption of this enzyme not only leads to the inability to form palmitate but also initiates the process of cell death in tumor cells.
The mice that were used in the study demonstrated no significant side effects like a change in weight or liver enzymes, which signifies that there is a possibility that a higher dose may produce better results without the fear of side effects. This does require more investigation, though.
It is possible that Fasnall may also prevent the development of drug resistance in breast cancer. It will be useful in reducing the dose of other drugs being used in the treatment of breast cancer and thus reduce their side-effects.
There is still a long way to go and a great deal of further research is required before the drug can be tested in human subjects, but this study supported by the National Institutes of Health and Pelotonia has opened new avenues in cancer treatment and possibly HIV treatment as well.
- Alwarawrah Y, Hughes P, Loiselle D, Carlson DA, Darr DB, Jordan JL, Xiong J, Hunter LM, Dubois LG, Thompson JW, Kulkarni MM, Ratcliff AN, Kwiek JJ, Haystead TAJ. Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2+ Breast Cancer. Cell Chemical Biology, 2016.
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