Personalized medicine, sometimes called precision medicine, has become a major buzzword in the pharmaceutical industry. For decades, scientists and physicians have puzzled over why some treatments are very successful for one patient, while other seemingly similar patients given the same treatment fail to get better. The idea behind personalized medicine is that by characterizing genetic factors, epigenetic information, levels of RNA expression, and other individual factors, we can better target our treatments to the people most likely to respond to them.
The Rise of Personalized Medicine in Cancer Treatment
Perhaps nowhere has personalized medicine been as transformative as in the realm of cancer treatment. More than 1.6 million new cases of cancer are diagnosed every year in the United States, reports the National Cancer Institute. Although the specific mechanisms underlying certain types of cancer may differ, all cancers are characterized by abnormal cell growth. Doctors use several forms of treatment, such as chemotherapy, immunotherapy, or radiation therapy to halt cell growth or decrease the size of tumors.
In the past few decades, our understanding of the genetic factors associated with cancer has increased dramatically. This information has been used to provide personalized medicine, tailoring treatments to those who may benefit most. For instance, certain forms of breast cancer are characterized by over-expression of the HER2/neu receptor. The drug trastuzumab (e.g., Herceptin, Herclon) is an antibody drug that targets the HER2/neu receptor. Tissue samples from breast cancer tumors are now tested for upregulation of the gene that encodes this receptor. Those whose cancer is Her2+ receive trastuzumab, which improves prognosis for Her2+ patients but not those who are Her2-.
Radiation Therapy Is Poised for a Personalized Medicine Transformation
Thus far, chemotherapy and immunotherapy have gained the most attention as cancer treatments transformed by personalized medicine. Radiation therapy, on the other hand, is delivered in much the same way that it always has been. Radiation therapy uses the energy from radiation to kill cancer cells. However, it is not specific to cancer cells, meaning that it also kills nearby healthy cells. This contributes to the prominent side effect profile of undergoing radiation, making it difficult for some patients to tolerate. With nearly two-thirds of cancer patients receiving radiation therapy at some point, improving its efficacy could have dramatic effects on treatment success rates.
Until recently, radiation therapy has taken a “one size fits all” approach to treating cancer. Now, however, radiation oncologists are looking to apply personalized medicine principles to radiation therapy. The gene activity profiles of different types of tumors are being investigated to determine which tumors are most susceptible to the cell-killing energy of radiation therapy. Scientists also aim to discover why some patients tolerate radiation therapy reasonably well, while others have severe and chronic side effects. Determining which patients are most likely to have serious side effects will assist doctors and families with treatment planning decisions.
Though the research in this area is only beginning, tremendous advancements have already been made in developing genomic models which predict treatment outcomes to radiation therapy. A study conducted at the Weizmann Institute of Science identified differences in expression levels of 113 genes between resistant and sensitive prostate cancer xenografts (1). The investigators expect that the genetic profile can be used to identify patients who may benefit from an alternative to radiation therapy.
Another team of scientists from the University of Alabama performed molecular analysis of genes involved in the response to radiation therapy as well as genes involved in response to a chemotherapy typically given in conjunction with radiation therapy to treat glioblastoma (2). These gene signatures could be invaluable in developing new treatment options.
These innovations need to be replicated in larger patient populations and are years from being incorporated into routine clinical practice. However, just as personalized medicine has revolutionized other aspects of cancer treatment, a rise in personalized medicine-informed radiation therapy could transform the landscape of cancer treatment.
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- L. Agemy, I. Kela, T. Waks, R. Pfeffer, A. Bar-Shira, A. Orr-Urtreger, E. Domany and Z. Eshhar, "Gene Expression Profiles Predict Sensitivity of Prostate Cancer to Radiotherapy," Journal of Cancer Therapy, Vol. 4 No. 4A, 2013, pp. 11-26. doi: 10.4236/jct.2013.44A003.
- Grunda JM, Fiveash J, Palmer CA, et al. Rationally designed pharmacogenomic treatment using concurrent capecitabine and radiotherapy for glioblastoma; gene expression profiles associated with outcome. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010;16(10):2890-2898. doi:10.1158/1078-0432.CCR-09-3151.