The Personal Cancer Genome and Precision CancerTrials

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April 8, 2014 3:10 pm

Clinical trials traditionally have been designed to treat patients with a specific disease and to treat allpatients on the trial the same way. For example, we would evaluate a new drug for breast cancer by givingthe agent to a group of breast-cancer patients, and if enough of them benefited, we would judge the drug agood one. If few patients benefited, the drug would likely be abandoned.

During such disease-based trials, a small number of participants, maybe 1-10 percent, can benefitamazingly from the drug, but further development of the agent is unlikely because clinical trials as usuallydone are impractical for small numbers of patients.

Genomics is now helping us understand why some patients respond differently to therapy; although all thewomen in our hypothetical trial have cancer of the breast, not all breast cancers are the same, becausethere is no routine cancer.

Traditionally, we diagnose breast cancer, leukemia or prostate cancer by examining the way cells appearunder a microscope. This tissue-of-origin approach has provided a histology-based or “microscopicclassification” of cancer that has been used for decades.

Histologically, malignancies such as breast and prostate cancer appear to be the same. But cancergenomic studies, such as The Cancer Genome Atlas, demonstrate that these cancers are dissimilar, withsets of mutations and other genetic changes that allow their grouping into subtypes (breast cancer mayhave more than 25). Each subtype may be a different disease that requires different therapy based on thetumor’s genomics. These molecular subtypes are driving the development of targeted drugs andinfluencing how we do clinical trials.

Some cancer centers, including the OSUCCC – James, are developing a new type of trial design that“baskets” different diseases that share a molecular target in one trial.

In some instances, if we know enough about the molecular subsets of a disease, we may be able to enrollpatients into trials that have a drug that matches the molecular makeup of their cancer. To facilitate thesetrials, cancer centers must be capable of providing a personalized molecular view of an individual’s cancer.

Gene sequencing technology called next-generation sequencing will enable oncologists to determinewhich of 200-plus significant genes are altered in a patient’s cancer and to use this information to guidetherapy. Ohio State is among the leaders in the country in promoting and championing this precisiononcology strategy.

Read “The Power of Genomics” to learn about the molecular differences in cancers.

By Sameek Roychowdhury, MD, PhD