My third day at the AACR Annual meeting was a day of phenomenal presentations. I am struggling to choose just one to tell you about because I attended multiple inspiring, thought-provoking, and even entertaining talks today. I decided to report on the plenary presentation by Steven A. Rosenberg entitled “T-cell therapy targeting unique cancer mutations” because I think this story has the most potential to positively impact patient outcomes.
A Featured Speaker Podcast by Friends of Cancer Research
Friends of Cancer Research aims to better understand the impact of assay variation on clinical outcomes, align standards, and define best practices for tumor mutational burden assessment. Harmonization of methods to quantify TMB will facilitate robust biomarker development and optimize clinical utilization and treatment decision-making.
Detecting & Managing Rare Pediatric & Adult Cancers
Neurotrophic tyrosine receptor kinases (NTRK) can become abnormally fused to other genes resulting in growth signals that can lead to cancer in many organs of the human body. TRK gene fusion-based cancers are rare but present in pediatric and adult cancers such as lung, thyroid, colon, etc. (see, e.g., Figure 1).
In a recent post, we discussed key considerations for designing a robust next-generation sequencing (NGS)-based lung cancer assay. Putting those plans into action in the development phase brings forth a new set of challenges. Through our experience developing NGS reference materials and the relationships we’ve built with assay developers of all stripes, we’ve identified those important factors and ways to navigate them. But before you begin designing and optimizing your assay, you should become very familiar with binomial and Poisson distributions and their use because the outcome of many analytical steps can be modeled and explained with them.
An important goal in cancer disease management is early detection. When detected early, disease progression can be significantly mitigated with a plethora of options (targeted therapy, chemotherapy, surgery, etc.) available to medical practitioners, to afford progression free survival and a higher quality of life. A great promise of liquid biopsies is the possibility of early detection of cancer long before clear evidence of lesions and tumor growth observable by imaging or other techniques.1 As proxy for solid tissue biopsies, plasma-based liquid biopsy application is rapidly gaining traction in cancer disease diagnosis, progression, monitoring, and in predicting resistance to treatment options.2
Next-generation sequencing (NGS) allows deeper insights than ever before into the human genome and a host of diseases and conditions. So it makes sense that there is a worldwide movement to employ NGS in a growing number of applications. But as the saying goes, with great power comes great responsibility.
Simply described, copy number variations (CNVs) are DNA segments present at a variable copy number in comparison to a normal genome. It was originally thought that a CNV consisted of a region of greater than 1 kilobases, however advances in technology have allowed for identification of CNVs as small as 50 basepairs1.
Clinical labs must constantly evolve their test offerings in order to support the most recent advances in clinical care. For next-generation sequencing (NGS) tumor profiling assays, there are often multiple commercially available kits with similar claims for gene content and sensitivity, as well as customized solutions. How can you quickly perform an effective evaluation of available assay systems to make a data-driven choice?
A 0.1% measurement requires a reasonable amount of input material
The field of circulating tumor DNA analysis (ctDNA, also sometimes called in a larger context “liquid biopsy”) holds great promise for monitoring response to cancer treatment, assisting therapeutic choice, monitoring recurrence, and for pre-cancer screening. As such there is a great amount of assay development and ongoing clinical trials; at ClinicalTrials.gov searching for the term "Circulating DNA" you can find over 180 open clinical trials for a wide range of tumor types and interventions.
Status of FDA regulation of laboratory developed tests, the promise of precision medicine, and a workshop about achieving accurate NGS laboratory test results
On January 23-25, 2017 the Precision Medicine World Congress was held in Mountain View, California. The PWMC conference kicked off with Dr. Keith Yamamoto, Vice Chancellor for Science and Policy and Strategy UCSF, with Dr. Robert Califf, FDA Commissioner in a “fireside chat” format. Dr. Califf has been with the FDA for 2 years, has served as Commissioner for 11 months, but has resigned as of January 20th 2017. One of his important parting thoughts presented was how the FDA has been re-energized by the >21st Century Cures Act to hire new scientific talent to implement the President’s Precision Medicine and Cancer Moonshot plans.