Doctors and patients have traditionally relied upon “one-size-fits-all” treatments and procedures, including chemotherapy, radiation therapy and surgery, aimed largely at fighting a particular type or origin of cancer (e.g. breast, prostate, pancreatic, etc) rather than target the unique nature of an individual patient’s cancer. This is despite one’s genotype having a profound influence on clinical responses to targeted anticancer therapies.

In fact, patients with the same cancer diagnosis not only are unlikely to share the same specific genetic variants but also unlikely to have similar reactions to identical treatments. Thus cancer must be viewed as a personal disease, with personalized treatments to best counter the disease.

Today, doctors are able to target the unique nature of an individual patient’s tumor, by matching treatments at the molecular level; resulting in improved outcomes. A recent study conducted by the CureMatch team found that patients with advanced cancers treated using the traditional or standard of care, which is based on their type or origin of cancer rather than their molecular tumor profile, had a mere 5% response rate to their treatment.

When patients with advanced cancers were treated using a personalized approach, matching them at the molecular level, there was a 27% response rate. This is personalized medicine. And it is available now.

Cancer has historically been treated using standard, single-drug therapies to target specific cancers, and even when using personalized cancer therapy, the vast majority of treatments are performed using targeted monotherapies. Though far superior to standard therapies in that a tumor’s genetic mutation is matched to a specific drug therapy, monotherapies are also deficient in that it is rare that a cancerous tumor has only one mutation that requires a matching therapy. Recently, it has been shown that when the right combination of multiple drugs is used to match multiple mutations, cancer treatment is more effective.

Each drug is able to target individual cancer mutations to improve treatment, and each drug can be used with the right dose to reduce side effects. Until now, matched combination therapy was not available outside of research, mainly because there are millions of possible drug combinations that are difficult for doctors to analyze. That is where CureMatch comes in. Our goal is to make matched combination therapy a clinical reality for oncologists and patients worldwide.

CureMatch’s personalized combination therapy approach can be illustrated using a simple example, using cancer cell lines derived from the tumors of patients. In a simple example, we show cell lines from human pancreatic adenocarcinoma tumors with eight mutations, two of which were “actionable” – meaning that these two mutations were known to be responsive to a specific drug.

Although the standard of care for this type of cancer is treatment with gemcitabine—the most commonly used chemotherapy in the treatment of pancreatic adenocarcinoma—the CureMatch platform instead recommended a combination of two specific drugs (“Drug A” and “Drug B”)* to simultaneously target the two actionable mutations.

In order to assess the efficacy of the recommended treatment, four scenarios were compared: (1) standard chemotherapy (gemcitabine); (2) personalized monotherapy using Drug A only; (3) personalized monotherapy using Drug B only; and (4) personalized combination therapy using both Drug A and B (the CureMatch-recommended therapy). A graphic representation of these four scenarios is shown below, with the two actionable mutations shown on the DNA strands as blue and white circles.

The effects of the drug treatments were measured using a cell viability assay, which measures the number of living cells remaining after treatment. Personalized Combination Therapy (the CureMatch-recommended therapy), at 1:1 concentrations of Drug A:Drug B, not only resulted in a significant increase in cell death compared to the matched monotherapies (3-5 fold increase), but also in a significant increase in cell death when compared to standard chemotherapy (>20-fold increase).

This in vitro data supports the notion that combinations of drugs specifically “matched” to actionable mutations present in a patient’s tumor have the potential to provide greatly improved outcomes compared not only to standard chemotherapy but to matched monotherapy. This the basis of the CureMatch approach.