Potentially a HUGE breakthrough !!! Liquid biopsies for lung cancer parients improves treatment (of tumors that are constantly changing their phenotype)

The “evolution” of tumor formation (carcinogenesis) symbolizes the quintessence of gene-environment interactions. The “biggest obstacle” (to the survival of a cancer cell) is how it can mutate and undergo epigenetic changes –– in order to survive chemotherapy and any other environmental adversity as a function of time. Cancer types are highly diverse, and they contain cells of many different types, with different genetic and epigenetic make-up. This allows cancer to adapt to changing environments, to survive treatments, and to spread (metastasize).

Researchers and physician-oncologists want to combat this fundamental lethal property to improve treatment, but –– to study tumor evolution in this way –– is to chase a fast-moving target. Investigators must track the genetic shifts in cancer cells, in real time, by setting up prospective assays that sample and analyze tumors during therapy. In theory, it should then be possible to tailor a growing arsenal of cancer drugs to fight emerging patterns of resistance and relapses. However, finding a way to do this –– in the least invasive way –– represents a formidable challenge, and one that cannot be accomplished by simply performing tissue biopsies.

There is another possibility: Over the past few years, interest has grown in developing techniques to analyze cell-free DNA in the blood, in the same manner as prenatal genetic testing is now carried out for fetal DNA in the mother’s bloodstream. As cancer takes hold, the blood fills with free-floating DNA released from dying tumour cells; these genetic fragments could be used to follow the evolution of the tumors from which they are derived. In a promising clinical study (see attached accelerated publication by Abbosh et al., just after the 1-page editorial), scientists report how they have done just that. What’s more, their trial design — incorporating prospective observations of these circulating fragments of cancer DNA — is a step towards implementing tumor-evolution monitoring as a clinical tool that can dynamically transform treatment..!!

These clinical data, and also a parallel RED-HOT preprint in the N Engl J Med (see attached; starting on p 27 of attachment) describe the results from the first 100 patients enrolled in a trial called TRACERx –– which aims to follow tumor evolution of people with lung cancer who are undergoing therapy. The Nature paper describes a test to assess and compare genetic changes in tumors and in the blood.

The dynamic tracking made possible by this “liquid biopsy” sequencing shows that early recurrence of the disease can be detected, and is associated with identifiable features in the circulating tumor DNA. The results of the analysis support the idea that such liquid biopsies could provide clinical benefit by simplifying procedures and allowing for more-intensive real-time monitoring. Clinical implementation requires additional long-term studies, so that the performance of this type of monitoring can be tested alongside therapy. This is starting to happen: the design of clinical cancer trials is evolving rapidly to accommodate biomarker testing, and a growing number of registered trials are in progress to prospectively monitor tumor progression in the blood. Still –– some challenges remain –– such as the feasibility and cost.

Nature 27 Apr 2o17; 544: p. 393 [ed]

C. Abbosh et al. Nature http://dx.doi.org/10.1038/nature22364; 2017

M.Jamal-Hanjani et al. N Engl J Med http://dx.doi.org/10.1056/NEJMoa1616288; 2017

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