Guest editors Christopher Abbosh and Charles Swanton discuss circulating tumor DNA as a potential biomarker for neoadjuvant treatment response in solid tumors…
Together with guest editors Charles Swanton, Sara-Jane Dawson and Chris Abbosh, PLOS Medicine is pleased to publish new research and commentary articles in a special issue devoted to early detection of and minimal residual disease in cancer. Below, Associate Editor Beryne Odeny interviews Aadel Chaudhuri, MD, PhD, co-author of two articles featured in this issue.
Please tell us a little more about your background. For example, your current role, where you’re based, your current research, and your scientific interests.
I am an Assistant Professor of Radiation Oncology at the Washington University School of Medicine, where I work as a Physician-Scientist. I have joint faculty appointments in Genetics, Biomedical Engineering, and Computer Science & Engineering which allow me to engage in highly collaborative interdisciplinary research. I’m also the circulating tumor DNA working group leader at Siteman Cancer Center. Science is both my hobby and my job, meaning I have quite a varied set of interests and find myself voraciously consuming scientific literature in my spare time.
I love answering highly translational questions in oncology using “liquid biopsy”, state-of-the-art liquid technologies for detecting cancer from bodily fluids like blood and urine. I’m particularly fascinated by the prospect of developing liquid biopsy through the analysis of circulating tumour DNA (ctDNA), DNA fragments in blood plasma that can be a powerful biomarker for early cancer detection. We and others have shown that we can detect tiny amounts of these ctDNA fragments, which we refer to as “minimal residual disease” before a cancer patient develops relapse. I’ve been using ctDNA and minimal residual disease detection to answer critical clinical questions like those presented in this issue of PLOS Medicine.
I’m excited that, in the future, ctDNA has the potential to touch every aspect of cancer care, from early diagnosis and screening, treatment response monitoring, MRD detection, tumor surveillance, all the way through to the tailoring of personalized therapies. As these liquid biopsy technologies continue to become more and more precise, we hope to be able to deliver cancer treatments more confidently across a range of different solid cancer types. I’m thrilled to be able to contribute to the scientific effort addressing these intriguing questions!
What inspired your studies on the use of circulating tumor DNA for early detection of malignancies?
I became interested in ctDNA for early detection of cancer when I was a postdoctoral scholar at Stanford University. I had the opportunity to lead an important study in which we showed that detection of ultra-low levels of ctDNA shortly after lung cancer treatment was highly prognostic of relapse, identifying residual disease months earlier than can typically be achieved with imaging. Arriving at Washington University three years ago, my goal was to answer similarly critical questions in the field of solid tumor malignancy, using ctDNA as an ultrasensitive analyte.
What were the main findings for the two papers you authored?
In our first study, we focused on malignant peripheral nerve sheath tumor (MPNST), an aggressive cancer that is associated with a hereditary cancer predisposition syndrome called neurofibromatosis type 1 (NF1). I teamed up with my colleague at Washington University, Dr. Angela Hirbe, and with Dr. Jack Shern from the National Cancer Institute. We found abnormalities in DNA copy number in blood plasma to be a powerful biomarker for accurately distinguishing MPNST patients from those without MPNST. Strikingly, we were able to see that DNA copy number in the blood could also be used to distinguish MPNST patients from NF1 patients with a benign lesion that is the precursor to MPNST. To my knowledge, this is the first ever demonstration of using a liquid biopsy technology to distinguish between cancer and pre-cancer in the context of all hereditary cancer predisposition syndrome.
In our second study, we measured tumor DNA in urine to see if we could detect residual disease before surgery for muscle-invasive bladder cancer. The standard treatment for this cancer is radical cystectomy, complete removal of the bladder and surrounding structures, a process associated with morbidity. I teamed up with two of my colleagues at Washington University, Dr. Vivek Arora and Dr. Zachary Smith. Our goal was to determine whether urine-based tumor DNA analysis could identify patients that respond well to chemotherapy delivered before muscle-invasive bladder cancer surgery. This important work could be extended in the future to help select patients who might be able to avoid the morbidity associated with radical cystectomy. We also performed novel analyses of urine to identify patients who in the future could be offered targeted inhibitors or immunotherapy in a personalized fashion.
What are the clinical and global implications of your work?
The implications of our findings are two-fold: Firstly, we have shown the potential to detect cancer at earlier timepoints than the current standard of care. By detecting cancer at an earlier and less severe stage, we can hopefully improve treatments and increase patients’ chances of survival. Secondly, the knowledge we gain from these liquid biopsy technologies should inform more personalized and precise therapy, perhaps mitigating the need for interventions such as radical cystectomy for bladder cancer or amputation for MPNST. While it will be important to formally validate the findings from our two papers here, we see these technologies as potential game-changers, with the promise of improving outcomes through earlier cancer detection and more targeted ctDNA-based treatment.
What is next? What are the most exciting developments in your field?
The next steps for me and my lab are to continue our projects developing and translating ctDNA technologies to answer important clinical questions. In addition to the work we’ve published here, some of the most exciting developments in the ctDNA field include using specific features of DNA (for example, epigenomic and fragmentomic analyses) for early cancer detection and for identifying the tissue in which a patient’s cancer originated.
What has been most enjoyable about publishing with PLOS Medicine?
The editorial staff are incredibly friendly and engaging. I’ve enjoyed getting to know them through the process of submitting our two papers for this issue. Also, I am pleased to be able to disseminate our work to the broad readership of PLOS Medicine. Finally, I’m very excited to publish in an open access forum, which makes it easy for readers globally to access and enjoy our work. It has been an honor and a pleasure publishing with PLOS Medicine and I look forward to similar successes in the future.
Image Credit: Aadel Chaudhuri