Never leave a cell behind

Print 20 January 2016
Lori Lesko / Cancer Research News, DDNews

SAN DIEGO—Targeted toward cracking the code to treating disease resistance in tumor changes, Epic Sciences Inc. has partnered with the Penn Medicine Abramson Cancer Center on multiple studies to explore biomarkers, identified by the analysis of circulating tumor cells (CTCs) at a single-cell resolution. This process is predictive of response to personalized cancer therapeutics—and a precursor to the future of oncology.

Detailed understanding of CTCs, which actively spread cancer to new sites in the body, provides insights into how existing medications work. Furthermore, knowing which resistant cancer subclones are present allows for better triaging of patients into personalized therapies right from the start.

“Successful treatment of cancer depends on understanding the heterogeneity of the patient’s tumor burden and the driving genetic alterations behind disease progression,” said Murali Prahalad, president and CEO of Epic Sciences. “Research conducted at the Abramson Cancer Center will enable faster development of novel personalized treatments that are able to address this heterogeneity.”

But the deal-sealer perhaps for the Abraham Cancer Center was in seeing Epic Sciences’ no cell left behind CTC detection and characterization platform, used to quantify the proteomic and genomic changes that accumulate in tumor cells over time and in response to successive rounds of therapy.

Following a simple blood draw, the Epic Sciences platform can reportedly detect all categories of CTCs in the blood and identify, on a single-cell basis, subpopulations of metastatic cancer cells that may be resistant or susceptible to cancer therapeutics.

Ryan Dittamore, vice president of marketing and translational research for Epic Sciences, tells DDNews, “Cancer heterogeneity, at the cellular level, will be a formative question for oncologists and drug developers for the next few decades.”

Such research is important, he says, “because a patient’s tumor can have heterogeneous subpopulations of cancer cells, each with distinct genomic variations and protein expression,” he said. “Some of these subpopulations may be small in number, but carry a stack of mutations that confer resistance to common therapies and may cause them to be aggressively metastatic.”

“Understanding the true cellular drivers of a patient’s cancer allows rational personalization of therapeutic plans—and, importantly, the selection of relevant patients for clinical trials,” he adds.

Epic Sciences’ no cell left behind technology is essentially a CTC detection and characterization platform that analyzes a regular blood draw from a patient, he said. A liquid biopsy provides a less-invasive means to analyze a cancer patient’s tumor than a traditional tissue biopsy.

“Epic Sciences employs a selection-free methodology to capture all nucleated cells, which enables the identification of CTCs present in the patient’s blood draw,” Dittamore explains. “This includes any unexpected but important tumor cell subtypes, such as those that may be small, clustered or lack certain epithelial markers.”

The unbiased view “allows for a more complete characterization of the full tumor cell population over time and in response to successive rounds of therapy,” he said. “The captured cells, which include CTCs and immune cells, are identified and assessed individually through immunofluorescence for morphology and protein markers.”

“Cells of interest can subsequently be individually isolated and assessed by PCR or single cell sequencing,” Dittamore notes. “These CTC profiles can then be used to generate signatures that can be the basis of companion diagnostics that match the right patients to the right therapies.”

A primary research goal in oncology is the concept of cellular heterogeneity, he points out, which is a very important reason as to why there has been no “silver bullet” for cancer.

“Our primary goal is to use our CTC detection platform to understand how heterogeneity affects the evolution of solid tumors as a result of therapeutic pressure,” Dittamore says. “This will increase our understanding of which cells are sensitive or resistant to specific therapies in the context to standard of care and novel therapeutic clinical trials.”

Epic Sciences has a CLIA-certified laboratory, which allows it to scale from small observational studies to large Phase 3 trials under one roof, he noted.

Since Epic Sciences uses a selection-free approach to isolate all nucleated cells, partners with banked samples can return to the samples in the future to interrogate them for novel cell types and biomarkers that were not known to science at the time. This has a transformative effect on the enduring value of a clinical trial, the ability to compare data between studies and recruitment in what often is a highly saturated patient population.

“Cancer is a complex, heterogeneous disease in which both genotype and phenotype change throughout progression,” echoes Erica Carpenter, director of the Circulating Tumor Material Laboratory and assistant professor in the Division of Hematology/Oncology at Penn Medicine. “We therefore need to utilize the most innovative technologies that allow us to study disease resistance.”

The research teams at the Abramson Cancer Center, a leader in the liquid biopsy field for cancer detection, will use Epic Sciences’ CTC detection and analysis platform to explore the heterogeneity of a diversity of cancer types, with a focus on genomic and phenotypic markers that help to better understand the utility of existing therapies and potential new drugs, according to Carpenter.

The Abramson Cancer Center is the cornerstone of the Penn Cancer Network, a select group of community hospitals throughout Pennsylvania, New Jersey and Delaware collaborating with Penn Medicine’s Abramson Cancer Center to provide excellence in cancer care throughout the region.

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