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Genomics already factors in cancer treatment decisions, but its role, along with the emerging fields of transcriptomics and systems biology is expected to burgeon over the near term. In a 2:30 p.m. symposium taking place Aug. 2 at the 69th AACC Annual Scientific Meeting & Clinical Lab Expo researchers from Columbia University and New York-Presbyterian Hospital in New York City will describe theirs and others’ use of these innovative disciplines might be further disseminated in practice.

Mahesh Mansukhani, MD, associate professor of clinical pathology at Columbia University Medical Center, will start off Precision Medicine Guided Pharmacotherapy in Cancer (34216) by talking about the pharmacotherapy of cancer, based on clinical whole exome, transcriptomic, and large panel mutation testing of tumors.

Julia Glade Bender, MD, an associate professor of pediatrics of Columbia University Medical Center, plans to discuss precision medicine’s role in the pediatric oncology clinic, and Alex Rai, PhD, DABCC, FACB, director of the special chemistry laboratory at New York Presbyterian Hospital-Columbia University Medical Center, will brief participants on biomarkers for precision medicine-guided therapy for prostate cancer.

Rounding off the the session, moderator Serge Cremers, PharmD, PhD, director of the clinical pharmacology and toxicology laboratory of Columbia University and New York-Presbyterian Hospital will discuss opportunities for therapeutic drug monitoring in precision medicine.

“Broader application of transcriptomics is coming down the road, including master regulator analysis to identify potential targets,” Cremers and his co-presenters told CLN Stat. Other methods to look out for include:

  1. Use of cell-free DNA for targetable mutation identification, early detection of resistance and recurrence, and monitoring of treatment; and
  2. Integrating genomic data into electronic medical records to mine for pharmacogenomic alterations and tumor-specific variants that may have become targetable after the initial interpretive report has been released. This integration also will facilitate clinical annotation of a large number of variants with currently uncharacterized significance. 

Precision medicine-based drug selection faces a number of major biological challenges, including tumor heterogeneity, and the lack of a targetable mutation for most patients. Access to drugs is an even more pragmatic challenge, as trials and targeted agents are extremely limited.

Because precision medicine for now remains mostly a hypothesis, issues exist with respect to third-party payer reimbursement for U.S. Food and Drug Administration (FDA)-approved agents, as well as for tests to identify potential targets for these drugs.

Beyond clinical validity, third-party payers are looking for evidence of clinical utility, the speakers told CLN Stat. “Off-label and compassionate use can be extraordinarily time-consuming and dependent on the willingness/ability of pharmaceutical companies to provide drugs and the regulatory burdens imposed by the FDA. Beyond access, there are also challenges with respect to monitoring drug levels and their effects,” they elaborated.

In pediatric oncology at Columbia University Medical Center, clinicians now order sequencing for every high-risk patient with an expected survival <60% at diagnosis and for all relapsed or refractory patients. This analysis involves a comprehensive platform that includes paired whole exome sequencing of tumor and normal tissue as well as the tumor transcriptome.

“Standard risk patients are generally not comprehensively sequenced at diagnosis, but rather have individual testing for known prognostic and therapeutic targets; however, their diagnostic sample is banked for potential future use,” the speakers stated. “Sequencing has provided clinically impactful information in nearly two-thirds of our patients by clarifying diagnosis, identifying actionable targets, or uncovering germline cancer predisposition.” 

These findings have been useful in directing patients to clinical trials or families to genetic counseling and testing so that proactive screening programs may be initiated for those at risk.

In the prostate cancer realm, clinicians, in order to personalize treatment strategies, also have been quick to adopt new tests that use biomarkers through noninvasive techniques. Multiple test options are available, all using genetic information to help tailor treatments based on patients’ individualized risk profiles. For those with advanced disease, for example, the use of molecular markers associated with treatment response is key to personalizing treatment.

New tests for these applications use liquid biopsy techniques such as circulating tumor cells, circulating tumor DNA, or exosome profiles to identify androgen receptor variants. “These biomarkers have been demonstrated to identify patients with resistance to abiraterone and/or enzalutamide, targeted agents that signal through the androgen signaling axis,” according to the speakers.

To attend this informative discussion on emerging methods of personalizing  cancer treatments and earn 2.5 CE hours, register now for the 69th AACC Annual Scientific Meeting & Clinical Lab Expo in San Diego July 30–Aug. 3.