By Dan Ryder
June 30, 2021
Tumor-Agnostic Therapy
Cancers are almost always targeted either by type or by where in the body they originated- but what if there were a more specific way to treat tumors based on their molecular signature instead?
This approach is called tumor-agnostic therapy and utilizes biomarkers to determine which drug to use for a given cancer. Cancers with the same genetic mutations can be identified using companion diagnostic tests that match the biomarker to the drug that targets it.
Tumor-Agnostic Drug
Roche’s Rozlytrek (entrectinib) is Roche’s first FDA-approved tumor-agnostic drug and is approved for use with two different biomarkers.
The drug is a selective tyrosine kinase inhibitor, specifically inhibiting tyrosine kinases A, B, and C (TRKA/B/C) as well as reactive oxygen species 1 (ROS1) proteins. The kinases are encoded by the neurotrophic tyrosine receptor kinase (NTRK) gene family, genes that are frequently rearranged and fused in cancer cells, allowing for uncontrolled growth. Similarly, genetic alterations of ROS1 produce aberrant growth and are frequently seen in cancer cells.
Biomarker Testing
Biomarker testing for Rozlytrek is for NTRK fusion-positive solid tumors and/or ROS1-positive non-small cell lung cancer (NSCLC). Treatment with Rozlytrek for NRTK fusion-positive cancer patients shrank tumors in 64% of patients and 73% of ROS1-positive patients, Roche’s researchers reported.
Remarkably, Rozlytrek was also effective in treating these cancers when they had spread to the brain, opening the possibility of further companion diagnostic work for brain cancers.
Personalized Medicine
Drugs like Rozlytrek are in the first wave of personalized medicine, an area that holds immense promise for both common and rare diseases, as evidenced by early successes of companion diagnostics in cancer treatment. Collaboration between bioinformaticians, geneticists, pharmaceutical companies, and physicians will continue to push the boundaries of biomarker use.
Dan Ryder, CEO & Managing Director, Bridge Informatics
Dan is the founder of Bridge Informatics, a greater Boston-based consulting firm that focuses on bioinformatics and software development. Bridge Informatics builds tools for life science with a concentration on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, he can be contacted at [email protected].
Sources:
https://www.roche.com/media/releases/med-cor-2019-08-16.htm
https://www.roche.com/products/product-details.htm?productId=e7ce2ea7-77a1-477d-9f2f-77c928c304be
https://www.roche.com/media/releases/med-cor-2020-08-03.htm
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/tumor-agnostic-therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859818/
https://www.gene.com/patients/disease-education/neurotrophic-tyrosine-receptor-kinase
