Personalized Cancer Therapy: Beyond Genetics

In cancer, personalized treatment largely centers on the use of drugs that target the effects of specific genetic mutations. According to a Nature Reviews Cancer article, however, the utility of this approach may have peaked because the mutations likely to respond to targeted drugs in a large number of patients have already been discovered. In its wake, researchers are turning to functional screening, a practical approach where the responses of cancer cells to drugs are evaluated to predict which drugs are most effective at treating an individual’s tumor.  

The success of functional screening is driven by methodological advances that make it possible to test drugs on live tumors. One advance, known as conditional reprogramming, increases the amount of cancerous and non-cancerous tissue sampled from patient biopsies while maintaining tumor heterogeneity (individual tumors can be heterogeneous when the cells of the tumor acquire different mutations). By keeping intact the heterogeneous cells making up a tumor, researchers are able to gain a more accurate assessment of how the tumor might respond to different cancer therapies. Another development, the improved isolation of circulating tumor cells, also increases the amount of cancer cells available for testing. Studies using enhanced volumes of circulating tumor cells for drug screening found that the tumor cells’ responses to chemotherapies were consistent with the actual clinical responses experienced in patients.

Further advances recognize the importance of a tumor’s environment in shaping a patient’s response to therapy. Scientists have developed what’s known as organotypic cultures that are better at mimicking tumor heterogeneity and the tumor’s environment than previous methods. Using this method as a basis, researchers have created algorithms that can predict with high accuracy patients’ actual clinical responses to drug therapy, suggesting a potential for use in predicting and guiding therapeutic choices.

By using a sample of a patient’s own tumor to test which cancer treatments are most effective, functional screening may represent the next step in personalized cancer care management. Though validation and tests of clinical utility are required before widespread use can begin, this approach holds great potential.

 

**To learn about tools Hopkins inHealth is developing to guide prostate cancer therapy, click here.

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