Cancer Genome Sequencing Will Mean More Targeted Therapies

As the cost of DNA sequencing plummets, the possibility of testing all cancer patients tumor genomes is becoming a reality. For just $1000 or so, a doctor might submit most any malignant specimen for a complete genetic work-up. The sample might be a core needle biopsy taken from a breast, a blood sample from a person with leukemia, or a snippet of a sarcoma removed in an operating room. In principle, checking a tumor for genetic changes should be straightforward, do-able.

But most cancer patients undergo surgery and other treatment long before their doctors consider sending a biopsy for full molecular evaluation. A recentpublishedsurvey among oncologists at two prestigious Boston teaching hospitals suggests that a significant proportion of specialists have a low level of confidence about their knowledge of cancer genomics. Aside from some kinds of lymphoma and leukemia, some lung cancers and a few other malignancies, examining cancer cells for genetic mutations is not routine in oncology practice.

Genomic testing of cancer cells seems like it should be available to all patients, said Lori Marx-Rubiner.At age 48, shes carried a diagnosis of metastatic breast cancer for five years. She lives in Los Angeles with her husband and teenage son, and blogs about her condition atRegrounding. Recently she took thehelm atMetavivor, a non-profit organization that promotes research inmetastatic disease.

Now I learn as much as possible about my condition and treatment options, she said. Marx-Rubiner, who holds a masters degree in social work, participates in scientific meetings and advocates for people affected by breast cancer. Most of her treatments so far have been selected to interfere with hormone signaling. Thats because her biopsy evaluated with old pathology methods when she received her initial, stage 2 diagnosis back in 2002 showed high levels of estrogen receptors in the tumor cells.Such an old approach didnt seem adequate for managing her case.

In the spring of 2014, she requested that her tumor be checked for genetic mutations. I wanted to see if I might be eligible for a CDK inhibitor or another targeted drug, she said. If Im going to take a risk on a new drug, I want the best shot possible.

But finding the specimen taken years ago and getting her insurance to cover the cost of genomic analysis proved challenging.After weeks of frustration and hassle, the biopsy sample was found and sequenced. The findings havent yet affected her therapy plan. She is soon meeting with a new oncologist.

Carolyn Hutter, an epidemiologist and co-leader ofTheCancerGenomeAtlas (TCGA), has been working on tumor genomics for some time. The TCGA project, a collaborative work by NIHsCancerandHuman Genome ResearchInstitutes, aims to characterize over 10,000 human tumors at the molecular level. Sequencing genes in tumor cells and seeing how those differ from a persons germline, or inherited DNA segments helps us to better understand the biological causes of cancer, she said in a phone interview. Its also useful because it can point to new targeted therapies.

One example of a tumor-specific mutation that can direct treatment is anALKmutation in lung cancer. Using this kind of genetic information about an individuals tumor is not futuristic, she considered. Rather, its happening today. Doctors are using DNA sequencing results to make decisions about therapy, to select targeted drugs, she said. Already the FDA has approved two drugs for patients who have lung cancer with ALK abnormalities in the tumor cells Crizotinib(Xalkori, Pfizer) andCeritinib(Zykadia, Novartis).

Within the next few years, people with cancer arising in other organs such as the breast, colon or pancreas, for instance might have their tumors checked for ALK and other mutations. Whether or not their malignancy is called lung cancer because the growth originated in the lung, they might choose a drug based on having an ALK or other genetic variant for which a targeted medicine is available.

Were coming up with new definitions of cancer subtypes based on molecular findings, Hutter said. Genetic profiling has wide potential, in terms of planning patients treatment and understanding prognosis in many cancer types. But I dont think well completely abandon tissue of origin as a way of categorizing tumors, she added.

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Cancer Genome Sequencing Will Mean More Targeted Therapies