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Personalized Combination Therapy: Curematch aims for multiple bullseyes

Personalized Combination Therapy: Curematch aims for multiple bullseyes
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Despite enormous advances in its management, cancer remains a significant and growing source of mortality. While a myriad of treatments exist, it is becoming increasingly clear that genomic alterations, which are different for different patients, have a profound influence on the clinical responses to therapies.

Most cancers harbor a cocktail of genomic alterations or mutations and it is these mutations, which can be highly variable and unique to an individual patient, that make cancer a truly personal disease. However, simply knowing what mutations are found in a patient’s tumor (as revealed by the molecular testing results) is not enough to design treatment options optimized for an individual patient and represents but one piece of a much larger puzzle that is personalized cancer therapy.

At CureMatch, we take the genomic information found in a patient’s molecular testing results to the next level. Traditional approaches to cancer treatment do not generally take into account the personal nature of cancer (usually due to the lack of such information, as only about 2% of cancer patients get their tumors profiled). In contrast, CureMatch actually exploits this knowledge and analyzes it using a unique multi-faceted approach to tailor combinations of drugs aimed directly at treating the distinct nature of an individual cancer.

CureMatch integrates and analyzes the molecular testing results using several manually curated and continuously updated databases compiled from published and obtained information in order to identify the impact of mutations on the function of the proteins and their interactions with drugs.

In addition, our analysis also takes into account: (1) the pharmacokinetic characteristics of the drugs; (2) interactions of the drugs with altered biochemical/metabolic pathways; (3) potential drug-drug interactions; and (4) potential drug toxicities.

In this way, unlike many other cancer resources available to cancer patients and their physicians (e.g., ClinVar, COSMIC, My Cancer Genome, CIVic), which provide important, yet limited, information on thousands of cancer-related mutations, CureMatch is not only able to characterize the mutations in the tumors, but our decision support system allows for the identification of: (1) all mutations within a tumor that can be targeted by a drug (i.e., the so-called “actionable mutations”); (2) the most efficacious drug combinations targeting all actionable mutations found in the tumor; (3) potentially toxic drug-drug interactions; as well as (4) potential drug toxicities.

Thus, Curematch provides to the patient and their physician, a ranked list of combinations of the smallest number of drugs targeting as many actionable mutations as possible, while eliminating/limiting redundancies and potential drug-drug interactions and/or toxicities. It is believed that such matched combination therapies targeting multiple actionable mutations simultaneously will not only improve the quality of life, but also provide significant increases in overall survival for the patient.

-Kevin T. Bush, Ph.D.

 

“Darts” flickr photo by Richard Matthews shared under a Creative Commons License

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