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Our Faculty Member of the month is Wafik El-Deiry, a Professor of Oncology at Fox Chase Cancer Center in Philadelphia, who specialises in the care of patients with colorectal cancer and those with rare genetic drivers of other tumour types.

Wafik is one of 40 active American Cancer Society Research Professors and he has over 400 peer reviewed publications. In this Q&A he talks to us about his preclinical and clinical therapeutics research.

Can you tell us about your work and research interests

I am interested in finding ways of enhancing cancer cell death and overcoming drug resistance in cancer therapy. As an oncologist I want to accomplish this with minimal toxicity to normal cells and patients.

My laboratory is focused on the p53 tumour suppressor pathway and its control of growth arrest and cell death. We discovered various downstream mediators of the p53 gene, such as p21 (a cell cycle inhibitor) and TRAIL receptor DR5 (a cell surface death receptor), and explored their role in signalling tumour suppression and in mediating the effects of cancer chemotherapeutics and ionizing radiation.

My laboratory is currently focused on drug discovery and development to enhance cell death of tumours. This includes tumours with mutated p53 as well as other drug-resistant tumours and gaining insights into immune modulation by novel therapies and therapy combinations.

We are unravelling drug resistance mechanisms including the role of hypoxia (reduced oxygen) in cancer therapy resistance. We have several promising small molecules that target mutant p53-expressing tumours where we are exploring anti-tumour mechanisms and its potential for clinical translation.

We are following up on our discovery of first-in-class TRAIL pathway inducer TIC10/ONC201 with mechanistic studies, understanding and overcoming resistance mechanisms and conducting studies with drug analogues.

What triggered your interest in oncology?

I became interested in oncology because I loved internal medicine and to be an oncologist involves taking care of the patient, which requires monitoring every organ system on an ongoing basis.

It is intellectually engaging, as we’re constantly solving many puzzles, and there is also the satisfaction from helping patients. For a physician-scientist, a career in oncology offers many research opportunities and life-long learning, which suits me very well as I am interested in how things work and finding better drugs to treat patients.

There is so much going on, and so much work to do in the field of cancer research and molecular oncology. The thrill of discovery, especially a great discovery such as p21(WAF1) early in my career cemented my interest and commitment to oncology and basic-to-translational research.

What do you enjoy most about your work as a physician-scientist?

There are many aspects of my work that are very enjoyable. Most importantly it is the opportunity to impact patients’ lives through the practice of medicine and through scientific discovery.

Interacting with patients and scientists on a day-to-day basis is richly rewarding as it bridges the gap between clinical and basic disciplines. A recent highlight was our basic drug discovery work on the small molecule ONC201/TIC10, which induces cell death in tumour cells, get translated in the clinic and seeing it directly benefit patients.

I feel very fortunate to be living through a great example of successful translation from bench-to-bedside. This includes discovery of the TRAIL receptor DR5, discovery of a TRAIL pathway inducing small molecule TIC10/ONC201, seeing the compound enter clinical trials and having patients with different tumour types benefit from the therapy.

In the clinic, I enjoy explaining cancer genes and drugs to patients as well as using modern targeted therapeutics to help patients live longer. On the research side, I enjoy mentoring and seeing trainees mature as investigators and become successful in their own careers. I embrace new technologies and have recently tested liquid biopsies to explore their utility in patient care.

Please tell us about one of the recent articles you recommended on F1000prime?

I was particularly fascinated and impressed by recent observations published by Goel et al. in Nature in 2017 that CDK4/6 inhibitors can stimulate an immune response against cancer in vivo. I picked the paper for F1000 because the results were unexpected; are broadly interesting to a large scientific and clinical community; and are timely with the recent intense interest in cancer immunotherapy.

Efforts to use cyclin-dependent kinase (CDK) inhibitors in cancer therapy go back more than two decades with current FDA approvals in breast cancer including palbociclib (Pfizer), abemaciclib (Eli Lilly), or ribociclib (Novartis) that are approved in combination with hormonal therapy. The article described the discovery of increased expression of major histocompatibility complex class I genes in tumour cells after cancer cell exposure to CDK4/6 inhibitors. The results have important translational implications for boosting immune checkpoint therapy through combination with CDK inhibitors, especially for tumours that are not particularly immune-infiltrated.

What advice would you give to those thinking about pursuing a career in STEM based on what you have experienced during your career?

The career of a physician-scientist can be extremely rewarding and satisfying. It is a privilege to care for patients. It is exciting to make discoveries in the lab and working to bring them to the clinic. Few careers offer the range of activities that include getting answers to fundamental questions about a disease like cancer; developing new tools to study it; or finding and bringing solutions including new drugs to impact on the lives of patients.

Such translational research can have a positive impact on the community and society-at-large. As you go through high school, college or graduate school, take the time to explore a career that combines science with medicine. There are so many options, for example a career that combines bioengineering with surgery, genetics with pathology, or various basic disciplines such as biochemistry, cell biology, microbiology or pharmacology with internal medicine or paediatrics.

The medical disciplines offer specialisation in areas such as oncology, cardiology, endocrinology, pulmonary medicine, GI or many others. Neuroscience can be combined with neurology, neuro-oncology or psychiatry among others. The permutations are vast and there are so many opportunities to find a great fit, niche, and pursue innovative, exciting and impactful work.