MiraDx, a Los Angeles-based company, is committed to discovering meaningful ways to better treat cancer in patients with mutations like and including the KRAS-variant. They are developing answers by applying their novel class of functional, germ-line genetic markers in both radiogenomics and cancer systemic therapy.
Radiation therapy is a form of cancer treatment that is used in over 75% of cancer patients diagnosed every year. While radiation is generally a safe treatment, 5-10% of patients will experience serious side effects from treatment. Additionally, the company reports, some patients respond not only locally to radiation, but also have an immune response that can help them to fight their cancer.
Miradx is a leader in this field with their radiogenomics program, applying their class of microRNA binding site mutations to identify patients that respond differently to radiation. Their first publication on this problem found that patients with the KRAS-variant have a weak immune response to radiation, requiring the addition of cetuximab to help (Jama Oncology, 2016).
Although it is completely logical that inherited, germ-line genetic differences, present in all cells, including those of the immune system, will predict response and toxicity to developing immune therapies, there has been little study of the genomic areas studied by MiraDx to find such biomarkers. MiraDx discovered a panel of such mutations that predict both response and toxicity to anti-PD1 and anti-PDL1 therapies currently on the market. They are working with potential partners to incorporate these findings into the newer agents to allow better patient selection to achieve improved response and less toxicity from these exciting new therapies. They are additionally working with partners to apply these mutations to all classes of developing immunotherapies.
Studies have definitively shown that KRAS-variant head and neck cancer patients respond differently to targeted agents used in standard treatment. Specifically, Cetuximab is an excellent choice for treatment. They are currently working towards additional collaborative studies to better define the time course and dosing, to make this the standard of care for these patients. Additionally, physicians and researchers at MDACC and Yale University have evaluated the association between treatment response for NSCLC patients in the BATTLE trials and the KRAS-variant. Results from these studies suggest that KRAS-variant patients respond to certain drugs, such as Sorafenib, and not others, such as Gefitinib, used in metastatic lung cancer.
For more information on MiraDX, visit their website.