The 7th Hallmark of Cancer is “Genome Instability and Mutation”. We’ve actually been alluding to this all throughout the coverage of Hallmarks 1-6. Cancer cells must evolve. They must evolve to outsmart our body’s surveillance and repair systems and get a step ahead of our normal cells. The way that they evolve is through acquiring mutations that give them a selective advantage. Here we talked about the tumor suppressor gene P53 and what happens when a mutation occurs and here we talked about how mutations in the BRCA gene lead to a significant increased risk of breast cancer. The mutation must give the individual cancer cell a selective advantage, but that advantage is what hurts the whole body. It allows the cancer cells to divide and spread unchecked.
Mutations in cells are an inevitable part of growing and living. Some mutations are random events and some are caused by inciting factors called carcinogens. Early on, I mentioned that this is the biggest difference between adult and childhood cancer. Most childhood cancers are the result of random mutations and no known carcinogens have caused the mutation – it’s just a random event that happened during the course of every day living. Many childhood cancers have distinct mutations that define them and there is hope that these mutations can be targeted like I discussed with TREK inhibitors and infantile fibrosarcoma.
It is now standard practice to look at the mutations in tumor samples to both help diagnose the patient and sometimes guide therapy. You may have heard the term “triple negative breast cancer”. This refers to the tumor lacking three mutations in receptors. The lack of mutations in this setting is actually a bad thing because we have drugs to target those mutations and the outcomes are better for patients with the mutations. The landscape of mutations and what we know about them is ever changing. One intense area of investigation is studying what mutations happen when a tumor comes back after initial therapy – are the mutations the same or different? If they are the same, why did the tumor come back? If they are different, how can that help us to cure the patient?
