Biomarker-driven clinical management of relapsed lymphoid cancers in the era of genomic medicine

Aim/goals:

The overarching aim of this proposal is to uncover the mechanisms of treatment failure, disease progression and treatment resistance in lymphoid cancers by performing comprehensive, multi-timepoint (temporal) genomic profiling of tissue biopsies collected from patients.

This will be achieved through 3 stages:

1. Stage 1) Retrospective genomic analyses and biomarker assessments of serially collected biospecimens at diagnosis and at the time of relapse. For this stage, tumor evolution and clinical courses of the two most common subtypes of lymphoma, follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) will be our focus.
2. Stage 2) Province-wide prospective biospecimen collection and genomic sequencing will be scaled up to allow all subtypes of lymphoma. For Stage 2, capacity building and clinical utility will be evaluated.
3. Stage 3) Development of a biospecimen processing, sequencing and reporting pipeline suitable for real-time decision making. Clinical validity of genomic/biomarker-based, real-time testing will be assessed, and implementation will be planned at this final stage and beyond.

Summary:

Collectively, lymphoid cancers are the 6th most common cancers in Canada, affecting patients of all ages. Advances in diagnostic accuracy and improvements in treatment have resulted in better overall survival for patients. However, when progression of disease occurs despite upfront treatment or an indolent lymphoma transforms  to aggressive lymphoma, mortality from the disease across virtually all lymphoma subtypes is very high, typically exceeding 80 percent. Improvement in outcomes relies on development and delivery of better treatment regimens, informed by validated biomarkers, requiring knowledge of the determinants of treatment failure and lymphoma transformation. The overarching objective is to improve outcomes of patients with lymphoma through translation of an improved understanding of disease progression/transformation into precision medicine approaches.