What is your lab/research focused on now?
The lab is focused on understanding different aspects of the mechanisms that lead to liver disease. We study how the liver heals and how it reacts to damage or to liver cancer. In this respect, we are focusing on the liver cancer micro-environment, that is, the niche in which the tumor grows and the cells that are part of this niche. How can we modify it, reduce the tumor progression, and improve the therapy? Our research group is also interested in defining the principles of best treatment of liver cancer, the determinants of therapeutic outcomes, and how we can improve access to the best care for all our patients. The growth of the number of researchers interested in all aspects of liver cancer and the high level of collaborative research at Yale is remarkable. I collectively refer to the researchers who come from many departments as the “commonwealth” of liver cancer research at Yale.
What inspires you to work in oncology?
Oncology is a fascinating field, one in which you can really feel the proximity between research and care. I have approached oncology from a different perspective, being primarily a liver doctor and a researcher. Among the things that brought me closer to oncology were seeing my patients develop liver cancer, working as a transplant hepatologist – some patients with hepatocellular carcinoma (HCC) can be cured with a liver transplant – and researching the mechanisms of liver repair and regeneration.
How has treatment improved for patients with liver cancer, and in your opinion, what is the outlook for liver cancer in the next five years?
Treatment of HCC has been transformed in several ways – including by progress in mini-invasive surgery, progress in loco-regional treatment, and the availability of liver transplantation. Contributing to this transformation more recently is the discovery of several pharmacologic agents that, alone or in combination, may provide hope for patients whose HCC is at an advanced stage.
I believe the next five years will demonstrate the value of adjuvant and neoadjuvant protocols in which surgery and loco-regional treatments are followed (or preceded) by the administration of associations of anti-neoplastic medication. I am confident that these regimens, particularly if including immune checkpoint inhibitors, will not only improve the response rate, but reduce the recurrence of liver cancer. Currently around 70% of patients experience a recurrence of HCC after the first successful treatment. Similar advances, although currently at a slower pace, will also occur for cholangiocarcinoma, the second most frequent primary liver cancer.
How do you translate your research into your clinical practice to help patients?
This is a difficult question because in an academic medical center, we do not appreciate a difference between research and medical practice. They are intertwined, they continuously inform each other. There is research in health care and health care in research.
Mentorship is an important part of laboratory research—how do you encourage collaboration and keep your team engaged and learning from one another?
Mentoring students, fellows, and younger colleagues is the essence of what we do at Yale. While we treat our patients and advance scientific knowledge, we also transmit what we know to those who follow us. And in doing so, we learn from our students and younger colleagues. We are stimulated by their questions, their curiosity, and their fresh views. The Liver Cancer Program at Smilow is a truly interdepartmental program, as it includes oncology, hepatology, surgery, radiology, pathology, transplant surgeons, and more. This allows a continuous exchange among different disciplines, enabling us to look at the same problem from many perspectives.
What would you say to a patient who may be hesitant to enroll in a clinical trial? What role do trials play in the care of liver cancers?
I would say that if they are being given an effective therapy, it is because others have participated in clinical studies. A clinical study is an opportunity for a potentially better treatment. The studies are carefully monitored, and patients receive the best possible care. However, the approach also depends on the patient’s personal history, motivation, and character.
What are some of the biggest challenges you face in caring for patients with liver cancer?
Treating patients with liver cancer is challenging, not only from a medical point of view, but from a social perspective, as well. Some of the major risk factors for liver cancer tend to fall on frail populations who have reduced access to care, to education, insurance and means. Providing for them is our daily mission.