Lymphoma-on-Chip, Technology to Study Drug-Resistant Tumors
Lymphomas, cancers that begin in the body’s immune (lymphoid) organs, have complex responses to treatments, and they often show drug resistance that is not well understood. This treatment resistance has deadly consequences. The most common lymphoma, Diffuse Large B cell lymphoma (DLBCL), has one subtype with as low as a 30 percent survival rate over five years.
New treatments are needed to improve clinical outcomes of the patients with DLBCL, but the role of lymphoma tumors’ microenvironment is still unclear. Current research platforms outside the body don’t mimic the true lymphoid microenvironment of the cells. They therefore can’t address lymphoma heterogeneity and varied treatment response across patients of the same subclass of tumors.
Ankur Singh, Mechanical and Aerospace Engineering/Biomedical Engineering, is developing and validating an experimental therapeutics platform— LETSSGo, Lymphoma-on-chip Engineered Technology for Single-Organoid Sequencing and Genomics—with funding support from the Innovative Molecular Analysis Technology Program of the National Cancer Institute. Singh has created LETSSGo to study lymphoma subtype-specific cells and patient-derived xenografts in a controlled fashion. In the resulting organoid, Singh is using DNA barcoding, genomic analysis, and the integration of drug-treated micro-organoids to determine tumor resistance across highly heterogeneous DLBCLs.
The technology could change the way scientists understand initiation and progression of lymphomas; enable mechanistic understanding of the role of tumor microenvironment and clonal heterogeneity; and provide prognostic values, increasing the predictive power of pre-clinical studies for drugs in development. It could also allow a faster and more rational screening and translation of therapeutic solutions.