April 23, 2019 | There is an urgent need to identify biomarkers that accurately predict for treatment response and guide the selection of novel combination therapies for patients who acquire resistance, says Helen Rizos, head of biomedical sciences at Macquarie University in Australia. Rizos is exploring the utility of circulating biomarkers as predictive and prognostic markers in melanoma, including circulating cytokines, exosomes and circulating tumor DNA.
On behalf of Diagnostics World News, Emily Le spoke with Rizos about the biggest challenges in immunotherapy and how biomarkers could help.
Editor’s note: Emily Le, a conference producer at Cambridge Healthtech Institute, is planning a track dedicated to Biomarkers for Immunotherapy at the upcoming Molecular Diagnostics Europe Conference in Lisbon, Portugal, May 6-9. Rizos will be speaking on the program. Their conversation has been edited for length and clarity.
Diagnostics World News: Hi Helen, can you tell us about your background and what you work on right now?
Helen Rizos: I have tried a few different areas of research during my career, including isolating bovine tRNA, investigating X-inactivation in kangaroos, and trying to make plants resistant to viruses. I always wanted to be involved in cancer research, however, and I moved into cancer cell biology for my first postdoctoral position and have worked in melanoma research for the last 20 years.
I have been fortunate to work closely with clinicians and scientists at Macquarie University, University of Sydney, and Melanoma Institute Australia. Our work includes the analysis of tumors and blood samples derived from melanoma patients during their treatment course—i.e. pre-treatment, on-treatment and if patients fail treatment we also try and examine progressing tumor and blood samples. This has been a wonderful translational program of research and we have contributed to a significant amount of work that has revealed why some patients acquire resistance to molecular targeted therapies and more recently, immunotherapies. At the moment we are particularly interested in the utility of liquid biopsies: What can they tell us? When should they be used? and Do they add value to current diagnostic and predictive measures? I am also interested in improving the detectability and sensitivity of circulating tumor DNA and also the more fundamental questions of when and why do cells secrete their DNA.
In your opinion, what are some of the biggest challenges in patient stratification for immunotherapy?
From my perspective, the challenge reflects the heterogeneity of cancer. In an individual with multiple metastases, we are assuming that each of these lesions will have a homogenous response, and that is not the case. If we accept intra-patient heterogeneity in tumor genetics, signaling and treatment response—then defining predictive markers is particularly challenging.
What do you wish to see more in the biomarker for immunotherapy field?
I would like to see a convergence of data that has been published to date, i.e. to apply and combine some of the promising, published biomarkers to large, collaborative patient cohorts. I know that when we try and apply some of these predictive biomarkers to our patient groups, we cannot validate their predictive performance. I would also like to see work on technological improvements in the liquid biopsy space—these biopsies have the clear advantage that they can gauge intra-patient heterogeneity in real time—but sensitivity is a real problem, and the fact that lesion location can also impact detectability hasn’t been studied sufficiently.
Do you think more researchers should make the connection between biomarkers for immunotherapy responses and immunogenicity?
I think this is a hot area of research, so many publications are coming out on predictive markers of immunotherapy response, it is interesting that the connection between toxicity and response is less well studied, however.