Clinical OMICs - Issue 8 - (Page 29)

Droplet Digital PCR™ enables liquid biopsy for monitoring cancer treatment. RAS-mutant cells-induced proliferation of chronic myelomonocytic leukemia (CMML). While vemurafenib shrank that patient's metastatic BRAFmutant melanoma dramatically, it also accelerated the progression of a previously unrecognized NRASmutant leukemia. Dr. Abdel-Wahab and his team's research, which was published in the May issue of Cancer Discovery2, set out to prove that combination therapy inhibiting the RAF and MEK pathways would not only treat the melanoma but would reduce proliferation of the patient's CMML. Through Genentech, they were able to arrange a single-patient investigational use of a promising but not-yet approved MEK inhibitor, cobimetinib. ddPCR was used to serially quantify melanoma-derived (BRAFV600K) and CMML-derived (NRASG12R) DNA in patient plasma over a 20-month treatment period. This technique proved essential for analyzing the regions of interest and determining the number of mutant copies at different times and under different treatment condiwww.clinicalomics.com tions. Using the information gathered from ddPCR alongside traditional assays-white blood cell counts and radiographic imaging-they identified an effective treatment regimen that beat back both cancers with less toxicity. This research foreshadows how ddPCR can contribute to the monitoring and adjustment of patient therapy according to molecular responses in the blood. While there remains a need for more testing and clinical validation of this biopsy method, Dr. AbdelWahab's research and other notable studies, demonstrate how ddPCR is paving the way for future success, given its ability to noninvasively and affordably interrogate the cancer genome with high levels of sensitivity and precision. References 1. Oxnard et al. Clinical Cancer Research 2014; 20(6):1698-705. 2. Abdel-Wahab et al. Cancer Discovery 2014; 4(5):538-45. TAMOXIFEN (continued from p. 5) "Using a gene signature defined by their differential expression after USP9X attenuation in the presence of tamoxifen, we were able to define patients with ERalpha-positive breast cancer experiencing a poor outcome after adjuvant treatment with tamoxifen," wrote the researchers. "The signature was specific in its lack of correlation with survival in patients with breast cancer who did not receive endocrine therapy. Overall, our findings identify a gene signature as a candidate biomarker of response to tamoxifen in breast cancer." Collectively, the researchers used data from about 680 patients from four different datasets to test the utility of the gene signature in predicting responses to tamoxifen therapy in hormone receptor-positive breast cancer patients. "We are currently validating our promising results using the data from a prospective randomized controlled trial, and we expect to complete this validation by the end of this year," said Dr. Bernards. "If this is successful, clinical implementation is a logical next step." In addition to being an e-publication, Clinical OMICs is a website. www.clinicalomics.com is updated frequently with relevant scientific advances, novel tests, new guidelines, and critical ethical and reimbursement issues. You can also access all the current as well as past issues in the archives tab. August 13, 2014 Clinical OMICs 29 http://www.clinicalomics.com http://www.clinicalomics.com

Table of Contents for the Digital Edition of Clinical OMICs - Issue 8

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Clinical OMICs - Issue 8