When talking about Personalized Medicine, one of the recent shining examples of this concept in practice is in the treatment of melanoma. Melanoma is a cancer of the pigment cells called melanocytes and is most commonly diagnosed as a skin cancer. The prognosis for melanoma is dismal when caught at later stages where the cancer cells have spread into lower layer of the skin or throughout the body (see the stats in the image below). Treatment typically involves surgery to remove the cancer cells, followed by chemotherapy and/or radiation therapy, but the response to these treatments is low.
There are two interesting personalized medicine examples for melanoma. The first is in determining whether a low stage (I or II) melanoma has a likelihood of spreading. Once a low stage melanoma has been removed by surgery, there is still a 14 percent chance that these patients will develop metastatic (melanoma that spreads) disease. To determine which patients are more at risk, a biotech company developed DecisionDx-Melanoma. This test looks at the expression of 31 genes and separates the patients into two groups based on the gene expression profiles. One group only has a 3 percent risk of developing invasive melanoma within 5 years whereas the other group has a 69 percent chance.
However, whether the cancer progresses or not, treatment is still an issue. That is, it was until a few years ago when scientists found that 50-60 percent of all melanoma patients have a mutation in the gene called "BRAF." This mutation tells the cancer cells to grow faster, so you can imagine that if you stop this signal telling the cancer cells to GROW, then they might stop growing and die. This is exactly what the drug PLX4032 (vemurafenib) does - it inhibits this mutated BRAF and stops the cancer cells from growing in 81 percent of the patients with this mutation (see the photo at the bottom of the post to see how dramatic this effect is). On the other hand, in patients without this mutation, the drug has severe adverse effects and shouldn't be used. Because of this, doctors don't want to prescribe this treatment to patients without the mutation. Therefore, scientists created a companion diagnostic. These are tests that are used to identify specific mutations before treatment to help decide what treatment to give. In the case of melanoma, this companion diagnostic tests if the patient has the BRAF mutation, and the patient is only treated with vemurafenib if they have this mutation.
This treatment was revolutionary with an incredible ability to cure melanoma. It was like melanoma was previously being treated with the destruction of a nuclear bomb, and now it is being treated with the precision of a sniper rifle - targeting the exact source of the cancer. So why is the word "cure" so obviously in quotes? Unfortunately, after continued therapy, the cancer relapses. Imagine treating cancer cells being like closing a road- it'll block up traffic (kill the cancer cells), but then you'll be able to find back roads that get you to the same place. In the case of cancer, the drug is targeting mutations in BRAF, and BRAF finds ways to evade the drug by mutating again (effectively removing the roadblock). Or the cancer cells themselves may have other routes besides mutated BRAF making the cancer grow. So although this drug is a life extender, scientists have been working to combine it with other targeted drugs (blocking off alternative routes) to make it a long-term life saver.
Dr. Cathy Seiler is the Program Manager for the tissue biorepository at St. Joseph's Hospital and Barrow Neurological Institute. She has her BA in Biochemistry and Molecular Biology from Boston University and PhD in the Biological Sciences from Cold Spring Harbor Laboratory. Her research and teaching focuses on genetics, cancer, and personalized medicine. Find her on Facebook at www.facebook.com/thingsitellmymom