BRAF/MEK alternative for metastatic melanoma
As cancer research progresses, more and more genetic mutations are being recognized as oncogenes, that (when activated), can activate the pathway(s) on which they are positioned, and move their cell to a cancerous state. This information is being used in two different ways. In some cases, patients are excluded from therapies where the agent doesn’t block their particular mutation (like KRas+ for NSCLC or colorectal cancer). In other cases, attempts are being made to inhibit these mutations (like EGFR+ in NSCLC, and BRAF+ and/or MEK+ in metastatic melanoma).
Where inhibitors have been designed, some (or some combinations) are demonstrating some success, but it has been observed that their efficacy can be lost lost if/when alternate activation routes are developed that no longer need the target gene to be activated in order to activate the pathway. In some cases, the inhibitor’s use can cause some toxicity.
There is another approach now being investigated in Phase II and III Trials, that has shown some success in treating any cancer with an activated KRas, NRas, EGFR, BRAF (and some other genes or receptors); and that approach is viral therapy, through which only cancerous cells are killed, and non-cancerous cells are not affected. Live viruses (either wild type or modified) are being delivered now by IV in Trials for metastatic melanoma, NSCLC, colorectal cancer, H&N, pancreatic, ovarian, sarcoma, and others. The virus can be used as part of a co-therapy approach with a platinum drug to dumb down the anti-viral immune response, and a taxane to make the entry to the tumor easier through its effect in making the vascular wall more porous. There are generally no significant side effects beyond a day or two of “pre-flu” symptoms that can be handled with Tylenol or equivalent.
One such viral therapeutic is Reolysin, from Oncolytics Biotech (ONCY). ONCY currently has a Phase II metastatic melanoma Trial in progress, and ONCY’s Investigator for their first line Phase II KRas+ NSCLC Trial will be presenting those Trial results at the “World Conference on Lung Cancer” in Amsterdam in early July.
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