Using Live Cells from Patients to Find the Right Cancer Drug

Today, many cancer patients benefit from targeted drugs that are matched to the distinct genetic mutations found in their tumors. However, especially in late-stage cancer, this “precision oncology” strategy has not proven to be as transformative as people once hoped. Here, Curious Dr. George asks Clifford A. Reid, PhD, CEO of Travera, how his company is addressing this problem.

Curious Dr. George: The U.S. Food and Drug Administration (FDA) has approved about 270 anti-cancer drugs. The National Comprehensive Cancer Network publishes guidelines for treatment of about 61 major cancer types. There is consensus on 1^st– and 2^nd-line therapy for most, but great divergence on best 3^rd-line treatment. Precision oncology based on population studies not only usually fails but is a false premise. What is Travera doing to convert the promise of effective and efficient targeted drug therapy into reality?

Clifford A. Reid, PhD: The original goal of what we now know as “precision oncology” was to understand the root genetic cause of each cancer, and then design a set of targeted drugs to attack each of these cancer-causing DNA mutations. At the time, this was called “personalized oncology,” and its promise was to deliver “the right drug to the right patient at the right time” based on the DNA mutations in each cancer. Unfortunately, this approach has not worked. While the cancer research community has identified hundreds of cancer-causing DNA mutations, drugs that target these mutations inexplicably don’t work for many patients that have the targeted mutations. To our great disappointment, the promise of personalized oncology is not being realized by these genetically targeted drugs.

A small part of the cancer research community has long recognized that it is simply impossible for the results of a clinical trial to generate personalized therapies for each individual patient. Clinical trials are fundamentally designed to include a population of “similar” patients, and get drugs approved for that population. But we know that cancers are highly heterogeneous, especially in late-stage patients, and that no “one size fits all” result of a clinical trial can address each individual patient’s unique cancer.

That part of the cancer research community has focused on developing tests that directly measure the response of an individual’s live cancer cells to a large set of cancer drugs. This direct-measurement approach not only incorporates everything we know about how cancers and cancer drugs work, but also incorporates everything we don’t know. It simply tries a variety of cancer drugs on each patient’s live cancer cells to find the drug or drug combination that will work for that patient at that moment in time.

While this direct-measurement approach may seem quite obvious, as it works beautifully for selecting the right antibiotics for patients with bacterial infections, it has never really worked in cancer, despite decades of efforts. The fundamental problem is that cancer cells, which are so robust inside a patient, become extremely fragile when removed from the patient, and typically die before most cancer drugs can be tested against them. Efforts to keep the cells alive long enough to test them have backfired: cancer cells forced to stay alive change how they respond to cancer drugs, and no longer behave like the cancer cells inside the patient.

Travera is the first company to develop a test that is fast enough to measure the response of cancer cells to cancer drugs without having to force the cancer cells to stay alive for many days outside the patient. Using a new measurement tool invented at the Massachusetts Institute of Technology (MIT), Travera measures the weight change of individual cancer cells in response to cancer drugs. It turns out that for most cancers and most cancer drugs, if the drug is going to kill the cancer cells in a few days, then it changes the weights of the cancer cells in a few hours, but by an amount too small to be detected prior to the MIT invention. Travera uses this exquisitely sensitive measurement tool to offer its Rapid Therapy Guidance test with 2-day turnaround time and high predictive accuracy. The test is now available for most cancers (including all carcinomas) and for over 100 FDA-approved cancer drugs.

For more information, please visit Travera at www.travera.com

Dr. Reid can be reached at creid@travera.com.