ctDNA and the Future of Lymphoid Cancer Research

In part, my research since joining the SFU faculty has been a logical extension of my PhD thesis. I continue to collaborate with many scientists and clinicians at BC Cancer to study the genetic features of non-Hodgkin lymphomas (NHLs), with emphasis on research questions that will make a difference for patients.

One of the cancers I focus on is diffuse large B-cell lymphoma (DLBCL), a common and aggressive form of NHL that is cured in many cases. It became clear during my early work that this cancer was very complex and each patient has a unique combination of mutations we refer to as “drivers”. If that wasn’t problem enough, we (and others at BC Cancer and elsewhere) have found that cancers often “evolve” during treatment, meaning the substantial number of patients who eventually relapse will have a tumour that may be genetically distinct from the tumour found at diagnosis. The Terry Fox Research Institute has provided my lab and the large lymphoid cancer research group at BC Cancer with funds to study this process of tumour evolution in DLBCL.

Another emphasis in the Morin Lab is exploring techniques to study tumour genetics that don’t rely on tissue biopsies. This is made possible, in part, because blood plasma contains variable amounts of DNA from tumour cells, known as circulating tumour, or ctDNA. But there are some difficulties in studying ctDNA, such as ensuring appropriate collection of plasma and developing tests to accurately detect and quantify the tumour DNA from these samples. Using a combination of new methods, we have shown that ctDNA changes often preempt a patient’s response to therapy and can indicate that a drug may not working.

Our ongoing work aims to study ctDNA from larger groups of DLBCL patients to better describe new mutations that may appear or disappear from a tumour while patients are receiving different therapies, helping their cancer cells become resistant to a drug.

Ultimately, this information may allow us to detect when a patient’s cancer starts to become resistant. ctDNA-based tests may also allow therapies to be selected to match each individual patient’s genetic profile. We are currently exploring this in collaboration with the Personalized Onco-Genomics (POG) Program.

Detecting key genetic features of ctDNA may become a diagnostic or prognostic tool. As technology continues to be improved and new sequencing methods become more pervasive, I hope that some of the techniques we use for research will be adopted into clinical practice.

Thanks very much for reading my blog this month!
Ryan