There is little doubt in my mind that technologies involving CTCs, liquid biopsy (see my thoughts from ASCO 2015) and digital pathology are going to converge. The ability to identify individual cells and specific mutations within those cells with high throughput algorithms will require appropriate detection of tumor cells through imaging techniques. This will shift the current paradigms of tissue preparation first, whole slide imaging second and image analytics third. Quantitative image algorithms will drive appropriate cell selection from liquid biopsy and subsequent mutation detection for appropriate therapies confirmed by tissue morphology, in some cases, as liquid biopsy will increasingly be validated not only for disease recurrence or progression but also for screening and primary diagnosis, in my opinion, in the future. Tissue will be complimentary for initial validation rather than primary in the future and fewer tumor diagnoses will require histology with liquid biopsies able to screen and diagnose and monitor treatment effects in near real-time offering multiple advantages over tissue biopsy collection and processing.
Just as signposts provide information, direction, and guidance, so too cancer biomarkers can better reveal the complex, dynamic, and heterogeneous landscape of malignancies.
Such information is critical for creating better cancer diagnostics, prognostics, and therapeutics, but the journey to find just the right biomarker is often a long and winding road.
Biomarker discovery and utilization is being explored by means of various methods and technologies. These include the isolation and characterization of rare circulating cancer cells, the use of multiplexing to extract information from limited amounts of sample, and even the application of evolutionary biology to detect early cell changes.
These approaches are all being developed by companies interested in improving cancer diagnostics, prognostics, and therapeutics. For example, one of the companies cited in this article is scrutinizing circulating tumor cells (CTCs) to predict resistance to cancer drugs. (This work was presented at a scientific retreat convened by the Prostate Cancer Foundation.) Other companies represented in this article are developing novel cancer diagnostic approaches. (These were detailed at the recent Cambridge Health Diagnostics Summit.)
While a typical blood sample from a cancer patient can contain 30 million nucleated cells, it’s estimated that perhaps only 5 of those cells may be destined to form tumors. “Most present-day diagnostic technologies cannot precisely detect those rare CTCs,” observed Ryan Dittamore, vice president, translational research and clinical affairs, Epic Sciences. “Identifying robust predictive biomarkers that can be utilized in real-time with a test compatible with diagnostic workflows is one of the greatest challenges to precision medicine.
“Epic Sciences is focused on developing sensitive diagnostic tests to characterize CTCs molecularly in order to match therapies to a patient’s cancer biology.” As Dittamore indicated at the Prostate Cancer Foundation event, the company evaluated its CTC approach in a study undertaken with Howard Scher, M.D., chief of the genitourinary oncology service at Memorial Sloan Kettering.
“We focused on a form of prostate cancer called metastatic castration-resistant prostate cancer,” explained Dittamore. “In the study, we confirmed the value of the prostatic cancer biomarker AR-V7 in 193 patient samples. In men with this androgen receptor (AR) splice variant, treatment with taxanes may be more effective than treatment with AR-signaling-directed agents (enzalutamide or abiraterone).”
In Epic Sciences’ “no cell left behindTM” approach, all nucleated cells from a blood sample are placed on a slide. CTCs are stained using biomarker monoclonal antibodies and assessed via immunofluorescence and high-resolution digital pathology scanning.
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