It was his Master’s degree thesis on intratumour heterogeneity that earned 24-year-old Diogo Maia e Silva the 2017 GAPIC David Ferreira Award. He began studying at the Faculty of Medicine of the University of Lisbon in 2011 and finished his degree six years later. He has been living in the USA since August 2017, working on his PhD in biological sciences at the Watson School of Biological Sciences, Cold Spring Harbor Laboratory. He has another four and a half years to develop his research work.

“Cancer is a generic term that encompasses many different diseases whose main manifestation is the growth of a group of abnormal cells, which form a mass (tumour) and often invade other organs. Tumours formed by cancer cells are not homogeneous: these cells have a wide variety of characteristics. For example, a certain subpopulation may show higher levels of a gene that promotes cell replication, while another may contain a genetic mutation that renders them resistant to the action of a specific pharmacology. We are interested in understanding how this heterogeneity determines their resistance to therapeutics against acute myeloid leukaemia, a type of blood cancer, and subsequent relapses.

Studying this problem in patients is very difficult. To work around this limitation, we use cell lines (tumour cells obtained from patients) that can be easily manipulated and maintained in cultures at the laboratory. Using acute myeloid leukaemia cell lines, we studied the response to various drugs and found that the mechanism of relapse differs depending on the therapies that are used. Specifically, the results we obtained seem to indicate that different therapies select recurrent tumour cells, responsible for cancer recurrence after an initial period of remission, in fundamentally different ways. While some chemotherapeutic regimens seem to select cells with permanent resistance “characteristics” (e.g., a mutation that lingers on daughter cells), predictable even before treatment, other agents seem to fail in a less deterministic way, making it harder to predict which cells will escape the treatment and relapse. These results, although far from any real clinical application, explain key aspects about the dynamics of leukaemia recurrence in response to several treatments. Simultaneously, by studying different therapeutic agents, we find that the combination of two regimens that are frequently used separately in the treatment of patients with acute myeloid leukaemia can prevent the malignant cells that survive the treatment from acquiring a permanent resistance, enabling the effective treatment of recurrent leukaemia, hitherto untreatable. If confirmed in other models, this result could form the basis for testing this combination in patients with leukaemia. We should note that, despite the fact that our observations are robust in cell lines, it is essential to validate them in other, more complex models, such as animal models.”

I wonder if, because of this heterogeneity, we run the risk of having “personalized cancers” and no effective collective treatments.

You are entirely right. No two tumours are alike, with exactly the same composition and genetic mutations. That is precisely the reason why the response to drugs is variable even in apparently homogeneous patient groups. To overcome this difficulty, the medical community is making a great effort to develop a “personalized medicine”, in which each patient is treated according to tumor-specific information, rather than with classical generic chemotherapies.

We came to know you because there is a Research Day on which the Faculty promotes the works of its best students. Initially, you intended to become a physician, but you are becoming a researcher instead. How important has GAPIC been in your career?

I feel a great sense of respect and gratitude for the group that works to offer FML students the opportunity to join a laboratory, experiment and, who knows, maybe fall in love with the world of scientific research. As the main responsible for fostering the critical spirit of scientific and medical research across the faculty, GAPIC plays a key role in supporting students and in liaising with FML-affiliated laboratories. Future physicians are often curious, and stimulating their scientific spirit is equally or even more important than the massive acquisition of knowledge inherent to their academic career.

Joana Sousa

Editorial Team