CRISPR for the development of organoids or PDX, and novel immunomodulatory, combination therapies. What our cancer scientists are eyeing in the coming year.
CRISPR-Cas9 in drug development and personalized therapy
Since the successful implementation of CRISP-Cas9 technologies it is a indispensable tool in basic as well as translational cancer biology. Applied for functional studies, CRISPR-Cas9 can be used for genomic editing and transcript knockdown to elucidate the mechanistic role of the respective gene of interest and/or target in drug development. Subsequent in vivo studies in genetically well-defined models such as patient derived xenografts (PDX) harboring the same genomic make-up can then be used to identify the promising candidate for clinical trials.
The successful deployment of these sophisticated genetic profiling technologies for comprehensive characterization of a patient’s tumor is generating detailed roadmaps for us to instruct the development of tailored in vitro or in vivo systems such as organoids or PDX. These methods will serve as personalized platforms enabling the identification of genotype-specific vulnerabilities. In a best case scenario, such personalized platforms could be studied in parallel to the patients, potentially allowing for the rapid identification of resistance mechanisms and the development of strategies to circumvent these limitations.
—Julia Schueler, DVM, PhD, head of in vivo operations at Oncotest,
a Charles River company based in Freiburg, Germany
Novel immunomodulatory and combination therapies
The number of experimental drugs approved to fight both blood and solid tumors by harnessing the immune system continues to grow. Some predictions estimate that by 2023 up to half of all cancer treatments will involve immunomodulation. These strides in immunotherapy continue to advance towards a durable, long term treatment for cancer. Currently, anti-CTLA- and anti-PD-1 antibodies have demonstrated unprecedented benefit for cancer patients. An additional 20-35 immunomodulatory receptors and ligands have been identified. Generating antibodies or drug compounds against these receptors and ligands will likely result in novel immunomodulatory cancer treatments. Moreover, combination therapies, utilizing either conventional treatments or vaccines, in unison with checkpoint inhibitors, will help determine the optimal blend employed for different cancer types. The ultimate goal is to expand the number of available combination strategies to treat more patients.
—Joe Murphy, PhD, Director of Science, R&D, for Charles River’s
Discovery Research Services site in Morrisville, NC,