Drug Resistance mechanism identified: New Hope for Improved Cancer Treatment

Drug Resistance mechanism identified: New Hope for Improved Cancer Treatment

In an article entitled, “MED12 Controls the Response to Multiple Cancer Drugs through Regulation of TGF-b Receptor Signaling”, published in November 21, 2012, issue of Cell 151: 937–950, the lead author Sidong Huang with twenty other associates from nine research groups have identified a key gene that determines resistance to a range of cancer drugs & shown precisely how the resistance develops, and suggests the possible ways to overcome. The study also reveals a biomarker that can predict responses to cancer drugs and offers a strategy to treat drug-resistant tumors based on their genetic signature. The team started out by investigating lung cancer cells that had become resistant to drugs targeting the ALK (Anaplastic lymphoma kinase) gene, which is hyperactive in around five in every hundred lung cancer patients. They found that, in many cases, a second gene called MED12 (Mediator of RNA polymerase II transcription) had become deactivated and this was causing drug resistance. Further experiments, exploiting an online ‘encyclopaedia’ of cancer cell data, suggested that this wasn’t limited to lung cancer cells with mutant ALK genes, but was a common feature of resistant cells from a wide range of cancer types, treated with several types of drug. Furthermore, the researchers also found that MED12 suppression caused drug resistance by enhancing signaling through the transforming growth factor beta receptor (TGF-betaR), a protein involved in cell growth and cell death. By inhibiting TGF-betaR signaling in MED12-deficient cells, they were able to restore drug responsiveness. The results suggest that TGF-betaR inhibitors, which are currently being tested in clinical trials, may counter drug resistance in cancer patients with MED12 mutations. It may be mentioned here that similar results have been reported in an article, Switching off cancer resistance in the 29th November issue of Nature (491: 641) by René Bernards of the Netherlands Cancer Institute in Amsterdam and his colleagues. They have identified a gene involved in resistance, and  also found a way to stop it in its tracks. This is indeed an exciting finding in the field of modern therapies  as it can target specific pathways in cancer cells,which often become drug resistant. [summarized by by a graduate student Samsad Razzaque of Plant Biotechlogy Lab, DMB, DU]

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