Liquid Biopsy Pioneers, Changing the Diagnostic Paradigm

May 24, 2017 | by City of Hope

Genetically targeted therapies are becoming standard in cancer therapy and clinicians at City of Hope are pioneering a new noninvasive way of obtaining samples to make strategic therapeutic decisions with less discomfort, and less risk to patients.

salgia-ravi-300x300 Ravi Salgia, M.D., Ph.D.

Liquid biopsy offers enormous practical benefits in both cost savings and patient well-being. Patients are saved the pain, inconvenience, risk and cost of an invasive biopsy, and additional biopsies can be taken easily as treatment progresses, since liquid biopsy involves only a venipuncture.

City of Hope’s Ravi Salgia, M.D., Ph.D., and associates conducted the first in-clinic investigation in nonsmall cell lung cancer patients to identify circulating tumor DNA (ctDNA) in peripheral blood using Guardant Health’s proprietary bioinformatics algorithms. Their data suggested that these free floating fragments of tumor DNA or biopsy-free ctDNA are a viable option for genotyping when there is insufficient material from a tissue biopsy or when invasive tissue biopsy is not an option.

Sumanta Pal 256x256 Sumanta Kumar Pal, M.D.

Another City of Hope physician, Sumanta Kumar Pal, M.D., and colleagues have recently conducted a similar study in patients with metastatic renal cell carcinoma (mRCC). This study is the largest of its kind and has been accepted for publication by European Urology

Liquid biopsy is Food and Drug Administration-approved for measuring intact circulating tumor cells (CTC), however the real excitement is in our ability to now understand, in real-time, the molecular changes that are occurring in tumor cells as a result of therapy. Since therapies target specific biomarkers, and these markers are constantly mutating in response to therapeutic pressures, serial liquid biopsies provide a noninvasive way to monitor treatment response.

This enables clinicians to quickly identify new mutations in ctDNA, which may be conferring resistance, and allow for rapid changes in drug strategy. Particularly in the context of resistance, ctDNA may detect mutations that are missed in a small tissue biopsy sample.

As a tumor stage increases, so to does the amount of ctDNA. In fact CTCs may not be detectable in early cancers but there may be detectible ctDNA. Identification of ctDNA may make it a useful tool in identifying subclinical and early-stage cancers.

Other City of Hope physicians are also using liquid biopsy to change the diagnostic paradigm.

Karen Reckamp, M.D., M.S., co-director of the Lung Cancer and Thoracic Oncology Program, is participating in a Guardant-sponsored study involving NILE (noninvasive lung evaluation). The trial is expected to provide data that will encourage the adoption of liquid biopsy as standard clinical care.

Jeremy Jones, Ph.D., assistant professor in the Department of Cancer Biology, is able to remove individual cells from the blood of prostate patients and individually characterize and assess their genomics. 
This technology will augment and perhaps even replace, in certain conditions, extensive imaging and invasive tissue biopsy, while offering improved outcomes and greater patient satisfaction.
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