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One of the greatest challenges in treating some advanced cancers is that they can evolve within an individual over the course of treatment.
A cancer forms when certain cells in the body develop 1 or more mutations that allow them to grow and divide faster than normal cells. These cancer cells have a great tendency to develop new mutations as the cancer grows. Within a cancer, there may be cancer cells with different mutations that lead to the evolution of new cancer behaviors over time, including different areas of cancer spread. This is called tumor heterogeneity.
Like Darwin’s “survival of the fittest” for animals, a cancer may have 99% of its cells be sensitive to chemotherapy or radiation, while 1% of its “fittest” cells are resistant. Therefore, with treatment, 99% of the cancer cells will die, and there will be a good clinical response of the cancer shrinking. However, the remaining 1% of cancer cells that are resistant to treatment will survive because they have a mutation that provides resistance to the treatment. These small numbers of cancer cells that are resistant to treatment can grow into a new cancer made of cells that are all resistant to the treatment that worked before. This process of a cancer becoming resistant to a previously effective treatment is known as acquired resistance.
One of the reasons that combinations of drugs or treatments are so often used in cancer is that when 2 or 3 treatments are used instead of just 1, the chance of cells having resistance to all of them is much smaller. In some settings, this makes it possible to potentially cure cancers that would have been much less likely to be cured with just 1 treatment at a time. However, combination treatments are more toxic to normal cells in the body as well, so the potentially serious adverse effects of killing normal cells need to be balanced with the beneficial effects of killing cancer cells.
Acquired resistance is the reason that many cancers become much more difficult to treat effectively as a patient progresses through different lines of treatment. The cancer cells that survived the earlier treatments are more resistant than the cancer cells that were present originally. At the same time, ongoing treatments may take a toll on a patient. Because of this evolution of increasing tumor resistance and the cumulative adverse effects of treatment, some people reach a point where further treatments may be more likely to cause harm than additional benefit. This point is different for each person, depending on his or her cancer and overall health condition.
How a Cancer Adapts: Key Clinical Implications From the Evolution of an Advanced Cancerhttp://cancergrace.org/cancer-101/2014/03/23/cancer-evolution-adaptation/
To find this and other JAMA Oncology Patient Pages, go to the Patient Page link on the JAMA Oncology website at http://www.jamaoncology.com.
Published Online: August 6, 2015. doi:10.1001/jamaoncol.2015.2199.
Conflict of Interest Disclosures: None reported.
West H(, Jin JO. The Evolution of a Cancer. JAMA Oncol. 2015;1(6):850. doi:10.1001/jamaoncol.2015.2199