Meet the Expert: Eugen Dhimolea, PhD.

Instructor in Medicine, Dana-Farber Cancer Institute

Eugen Dhimolea, a cancer biologist, is a multi-faceted researcher with experience in various types of cancers and related mechanisms of drug resistance/persistence. His research expertise encompasses complex 3-dimensional organoid cultures, stroma-tumor interactions and experimental therapeutics. With his finger on the pulse of cutting-edge research, we talked to him about his passion for cancer research and what he sees for its future in the next five to ten years.

Your education and research background are extensive. Could you give us an overview?

 I obtained my PhD at the University of Athens, Greece, where I began my journey in cancer research. During my thesis I studied the mechanisms of response to hormonal therapies in breast cancer and the development of biomarkers to predict the response to therapy in this cancer type. I continued my post-doctoral work at Tufts University, where I focused on the role of tumor microenvironment on cancer cell biology and morphogenesis in normal tissues and in cancer. Following that, I came to Dana-Farber Cancer Institute/Harvard Medical School, where I am a junior faculty member. Here, I study the mechanisms of drug response and resistance in various tumor types, such as breast and prostate cancer.

Could you provide some insight on your research work at Dana Farber Cancer Institute?

At DFCI I’ve focused mainly on the role that the 3-dimensional tumor architecture and the elements of the tumor microenvironment have on the response of tumor cells to various cytotoxic cancer drugs, such as chemotherapies. In particular, I am interested in the features of the cancer cells that persist in the body after treatment and how we can eliminate them in order to achieve cures. I have also dedicated significant effort into the development of new technologies – especially cancer organoid-based technologies and culture systems – as drug-screening systems in cancer and tools for personalized medicine.

Where do you think cutting-edge research into the cancer constellation of diseases is going to take us in the short term, say the next five to 10 years?

That’s not an easy question. For instance, 20 years ago few people had predicted the recent breakthroughs in areas such as immune-oncology; yet this sub-field has revolutionized cancer research and treatment over the last 10+ years. For now, I would say that the past decade’s progress in immuno-oncology will continue because of very solid proof-of-concept achieved by such treatments. So, progress in that space is likely to continue.

While predicting breakthroughs is risky, I think it is likely that we’ll see significant advances in the fields of genomics and genetically-defined cancer drivers, as well as the development of drugs that target novel targets in the cancer epigenome. Also, I would say that we are gaining a better understanding of the microenvironment and its role in carcinogenesis and in supporting the viability of cancer cells; therefore, new drugs that target the tumor microenvironment will also likely be pursued in the next few years. Lastly, there is a renewed interest in cancer cell state transitions during drug treatment (including cancer cell dormancy), and the development of therapeutic approaches targeting these molecular switches.

Could you share your insights on immuno-oncology’s potential for future treatments – where do you see the most likely advances coming from?

For the past 10 years, the field of immuno-oncology has made great strides in improving the clinical outcomes for cancer patients. This research area remains very dynamic, with continuous improvement of existing approaches and new technological and conceptual advances. I expect further progress in cellular therapies such as new, sophisticated, CAR-T constructs. Another potential advance may be the introduction of off-the-shelf cellular therapies, which will greatly facilitate the manufacturing process and lower the cost of these therapeutics. Finally, another highly promising approach is that of personalized cancer vaccines targeting tumor neoantigens, which leverage our capabilities in cancer genomics in order to unleash the immune system against the cancer cells.

Could you speak about the use of new technologies in cancer research?

Advanced cancer models, for example cancer organoids and organoid technologies in general, realistic in-vitro systems, and more complex animal systems that mimic cancer at the organismal level, will be instrumental in the development of therapies against this disease. New methodologies that can be used to interrogate cancer cells at the genomic, epigenomic and protein levels will increase the amount of information and understating about the basic biology of the disease. Overall, the technological progress in pre-clinical research is going to be important for the development of breakthroughs at the bedside.

Can you elaborate further on the pre-clinical modeling techniques you mentioned? How do they work, and how would cancer researchers employ these models?

Cancer organoids are in vitro, miniaturized, 3-dimensional versions of patients’ tumors; essentially a living personalized cancer model. To a large degree they preserve the genetic makeup and architectural characteristics of the original tumor; therefore they’re considered a much more realistic model of cancer biology. Currently, cancer organoids are being used in biopharmaceutical research to evaluate drug candidates, such as in high-throughput screening applications. Additionally, cancer organoids are also applied in personalized medicine to test dozens or hundreds of potential drugs on a patients’ tumor cells in order to design the optimal therapeutic regimen.

Does any of your research involve or include AI-based technologies?

I don’t develop AI tools myself, but we do collaborate with AI scientists to generate machine-learning approaches that could help address complex biological and clinical questions.

What is it about working with cancer that attracted you in the first place?

First of all, it’s a devastating disease for patients and their loved ones. It’s still a puzzle with a thousand pieces; therefore working in the cancer field touches upon many aspects of biology in general. Working in cancer is to say that you may work on many different facets of biology and medical research. Because the nature of the disease is so complex, you are always trying to find answers through interdisciplinary exploration of various fields such as genetics and epigenetics, development, chemical biology, drug delivery, etc. The goals of answering the persisting complex scientific questions and addressing this high unmet medical need are the reasons that I stay in the field of cancer research.