The intra and inter-tumoral heterogeneity within a tumor manifests by means of different cell populations (cancerous and native) and their respective microenvironments co-existing in a surgically resected sample. Most of the data analyzed and abstracted from these often-scarce samples, have information on the target cells diluted with non-target cells. With the microfluidic probe, a completely new line of investigations may now be feasible, by providing a platform to perform localized biochemical reactions.

Microfluidic probe: The MFP is a non-contact, scanning technology, developed at IBM, which spatially confines nanoliter volumes of chemicals hydrodynamically on biological surfaces at the μm-length scale. The MFP is being developed with a view to insert technology within the pathology work-flow, in particular the molecular work-up of tumor biopsies for targeted therapy.

Non-small cell lung carcinoma (NSCLC): NSCLC is the most common form of lung cancer, which shows complex heterogeneity. Among the currently therapeutically targetable genomic alterations in NSCLC, we will focus on profiling tumors for v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations specifically type V600E2 in the adenocarcinoma subtype, and discoidin domain receptor 2 (DDR2) mutations in the squamous cell carcinoma histotype. These molecules have been implicated in epithelial-mesenchymal transition (EMT), a mechanism by which cancer cells acquire a migratory phenotype. These molecules are thus important tissue microenvironment interactors. Elucidating their signaling networks at invasion fronts may provide insight into tumor progression and chemotherapy resistance.

The MFP will leverage analysis at the μm-length scale to analyze tumor heterogeneity based on different NSCLC histo-subtypes, the tumor epithelia versus surrounding stroma and investigate the tumor invasion front versus tumor center. Multi-modal investigations of the tumor at the genetic and proteomic level will likely increase our understanding of the tumor microenvironment.

Localized analysis biopsy vs. surgical specimen

Soltermann et al. Clin Cancer Res 2008, Tischler et al. Mol Cancer, 2011, Morra et al. Lung Cancer 2012