Développement précoce de nouveaux traitements pour le lymphome à grande cellule diffuse et la leucémie myéloïde aiguë

 

Sarit Assouline

CIUSSS de l'Ouest-de-l'Ile-de-Montréal

 

Domaine : cancer

Programme Chercheurs-boursiers cliniciens - Senior

Concours 2018-2019

My overriding goal is to improve the survival of patients with leukemia and lymphoma by identifying and testing novel therapies.

Improving the outcome of patients with relapsed diffuse large B cell lymphoma (DLBCL), a genetically diverse and mostly deadly disease, requires and multipronged approach. I discovered that panobinostat can produce unusually long remissions (exceeding 5 years) and that mutations in MEF2B correlated with response. I will validate this finding in a larger patient cohort and with cell line models. While panobinostat did not cure all patients, my preliminary data suggest that it alters the sensitivity to checkpoint inhibitors in non-responders. These therapies have revolutionized cancer care, and efforts such as mine are needed to enhance their effectiveness. Lastly, I am testing venetoclax, a BCL2 inhibitor, in combination with chemotherapy for patients with relapsed DLBCL, where BCL2 is commonly expressed and causes chemotherapy resistance.

Some acute myeloid leukemia (AML) over-express the oncogene, eIF4E. For 11 years I have tested ways of targeting eIF4E in patients. Now, through extensive genomic profiling, I want to operationalize and align the definition of AML with high eIF4E with known WHO AML subgroups, to clearly identify those patients in whom targeting eIF4E will be curative. Also, we have recently discovered that eIF4E causes leukemia cells to be coated with hyaluronic acid, which confers a growth advantage, a property previously only attributed to solid tumors. Remarkably, ribavirin reduces this coating, as does the enzyme hyaluronidase. Given together, these drugs result in even less coating and the cells die. Thus, I will test ribavirin and hyaluronidase in AML patients, an extremely novel approach to AML therapy.

I have developed a research niche, where I use my expertise in clinical research and epidemiology to move from collaborators' laboratories to patient rooms and back, to make novel and inspiring discoveries.