Discovery and Development
Clients of Molecular Response Laboratories include pharmaceutical and biotechnology companies that need clinically relevant models to screen oncology compounds and make decisions about which ones to advance, and which patients should be included in their clinical trials.
Dr. Broudy says the tumor bank helps with many of the stages of drug discovery and development including target identfication, target confirmation, patient selection, lead optimization, candidate selection, combination agent selection, indication expansion, and the holy grail of personalized medicine—companion diagnostic inclusion/exclusion testing (which the company performs in its clinical CLIA/CAP laboratory).
Molecular testing platforms the company uses include whole-genome microarray profiling, qPCR, fluorescent in situ hybridization, flow cytometry, and immunohistochemistry.
The in-house clinical testing lab at Molecular Response develops molecular tests based on novel mutations to evaluate drug responses. Among the newest is a clinically validated BRAF test that detects the V600E mutation found in ~50% of melanoma patients and 15% of colorectal cancer patients. The PCR-based test shows good sensitivity and sample acceptance, according to Dr. Broudy.
“We’ll be able to tell more patients if their tumor harbors the mutation, and they can use that information with their doctor to make better therapeutic decisions,” he says. The FDA has approved drugs that target BRAF mutations, such as Roche’s recently released Zelforaf™ (vemurafenib) for treating melanoma patients with the BRAF V600E mutation.
“The big question is ‘what will be the next BRAF for the next vemurafenib?’” says Dr. Broudy. “That’s where high-quality, clinically relevant, patient-derived models come in.”
To further characterize the development of novel therapeutics, Molecular Response Laboratories identifies or verifies mechanisms of action, as well as pharmacodynamic and predictive molecular markers. The company performs these analyses using its PDX mouse models, as well as through an ex vivo platform that marries 3D cell culture with high-content imaging. The ex vivo platform is a complex culture system that provides tumor cells with a growth environment much more similar to the original in-human setting—a key aspect of translating preclinical findings into clinical reality, says Dr. Broudy.
Other companies team up with Molecular Response Laboratories to make better oncology screening tools, he adds. A recent collaboration with Transparent in Chiba, Japan, resulted in a 3D cell culture system based on Transparent’s 3D cell culture plate design and Molecular Response Laboratories’ bank of living tumor cells. Transparent markets the product under its Cell-able Oncology™ brand, which allows primary tumor cells to grow in 3D cultures that closely resemble in vivo like conditions.
Pharmaceutical and biotechnology companies that team up with Molecular Response Laboratories enter into a collaborative partnership. “We work alongside our partners to move their compounds along the clinical development pathway,” says Dr. Broudy.