Guest Column | December 29, 2020

Research Drives Progress In Precision Medicine

By Robert L. Coleman, MD, chief scientific offer, US Oncology Research


One of the most significant advances in oncology over the past several decades is precision medicine – the use of therapies targeting biological abnormalities associated with carcinogenesis. A giant leap forward in this effort occurred in 2005 when the Cancer Genome Atlas launched, which was a multidimensional collaborative effort of annotated descriptive analytics of the cancer genome. The Cancer Genome Atlas was inspired by the emerging realization that a much more holistic understanding of oncogenesis would have the greatest impact in driving innovation, particularly with respect to therapeutics. This effort did not disappoint; the publicly available databases provided the necessary resources to enable hypothesis testing and discovery, which along with biomarker development has accelerated the realization of patient-drug matching and ushered in the beginnings of precision medicine.

Since then, much has been learned about the role of biomarkers in tumors, leading to the development of many life-changing therapies. None of these advancements would have been possible without research — the foundation for the tremendous progress in individualized targeting therapy.

Precision medicine trials hold great promise in producing the most meaningful results. These trials investigate patient and tumor characteristics believed to be relevant for a new therapy’s efficacy. In special situations where the biomarker serves a predictive function (as opposed to only prognostic), our expectation would be that selected treatment would only work in those identified patients, thereby sparing biomarker-negative cohorts unnecessary exposure.

Research Fuels Precision Medicine, Improving Survival

Today, perhaps more than ever, comprehensive preclinical and clinical research integrate to produce the framework through which the concept of precision, or “individualized,” medicine can be validated. Preclinical research, where hypotheses are tested, narrows the output that eventually results in clinical trials. The understanding gained preclinically over the last decade has led to many new compounds and given new life to old ones. These breakthroughs resulted in dramatic improvements in outcomes. For instance, recent observations from immunotherapy trials have demonstrated strong efficacy in  patients with certain cancers, such as melanoma and B-cell acute lymphocytic leukemia, that have not responded to treatment and/or where the cancer recurred after traditional therapy.1,2 In many cases, immunotherapy generates responses, some dramatic, as well as durable remissions.3,4,5

Poly ADP-ribose polymerase (PARP) inhibitors have also recently emerged on the treatment landscape for certain tumors, particularly those associated with homologous recombination deficiency. The results have literally been life-changing, especially for advanced ovarian cancer patients, who are now living longer than ever. While survival data is still maturing, some patients are alive and well after 10 or 15 years.

Remarkable responses have also been obtained for various rare diseases, particularly those where the oncogenic switch is defined by single gene activating mutation/alteration. For example, impressive results have been seen against cancers linked to NTRK fusion mutations, as well as gastrointestinal stromal tumor disease, a cancer universally fatal in the past. Additionally, there are now very effective drugs that extend survival for ALK positive lung cancer patients. Many more breakthroughs could be mentioned, as the list is growing rapidly.

As intimated, nearly all these cutting-edge therapies are associated with a predictive biomarker — findings in a tumor that define the cancer process in certain patients. When a specific drug is given targeting a biomarker, a benefit is only seen in a patient who has that particular alteration. This approach is very individualized and personalized, which is the goal of precision medicine.

Cost Reductions Are On The Horizon

Not unexpectedly, novel drugs that underscore precision medicine therapy are usually quite expensive. During the early stages of development, cost is generally not a mitigating factor. After the drug becomes available to the general public, however, costs must be addressed. Ultimately, when multiple drugs enter the market and compete, costs usually decrease. Biosimilars may also be developed, which are cheaper than the original innovator drug.

Meanwhile, costs can be decreased by only administering drugs to patients who will truly benefit from them, rather than to those who may not see a gain. Ensuring the right drug is paired with the right patient will reduce costs by eliminating unnecessary treatment while optimizing the benefits patients receive.  

Giving the right patient the right therapy at the right time is the goal of all stakeholders in the healthcare industry. In particular, biopharmaceutical companies are critical partners to providers in meeting this goal. In most cases, it is biopharmaceutical companies that are driving and funding clinical trials. Therefore, they are essential in our development of precision medicine trials. We need to work together to navigate therapeutic strategies, and our pharma partners should broaden their spectrum of support when precision medicine identifies sequences or combinations that may not involve their assets. We all must have a patient first mentality.

Clinical Trials Are Critical

Precision medicine is moving ahead in leaps and bounds in the battle against cancer. Research is continually identifying more biomarkers, leading to promising new treatments. But these exciting new therapies will never happen without a concerted effort from all stakeholders to drive and support clinical trials. My urgent call to all providers is to enroll patients in trials whenever possible. These studies address very important questions about how to improve the standard of care, and many of them will play a vital role in bringing the promise of precision medicine to more patients.

For example, US Oncology Research is making clinical trials available and operational at the community level. Our contribution is to provide support so busy clinicians can participate in research and place patients on studies. This allows patients all over the country to participate in precision medicine trials, among others, which is pushing research forward.

The tumor microenvironment is a dynamic and complex ecosystem that is rich fodder for ongoing discovery, raising new hypotheses and identifying opportunities for clinical medicine. However, it is incumbent on us to do our homework to understand critical processes for oncogenesis, determine whether or not alteration, activation, or blockade can lethally alter the natural history, and demonstrate that these treatment strategies can be safely administered. This is truly exciting and gives hope and promise to many patients.

We are no doubt moving in the right direction. Do precision therapies apply to all tumors? Not yet, but as we learn and discover more, we are chipping barriers away one at a time.



About The Author:

RobertRobert L. Coleman, MD, is the chief scientific officer at US Oncology Research. Prior to joining the company, he served as professor, vice chair for clinical research, and executive director for the Cancer Network Research Program at the University of Texas MD Anderson Cancer Center. Coleman’s research interests include drug discovery and novel therapeutics for ovarian, uterine, and cervical cancer; clinical trial development; and statistical design. He has served as PI or co-PI for several Gynecologic Oncology Group (GOG) prospective clinical trials and currently serves as president of the International Gynecologic Cancer Society. Coleman has authored or coauthored over 600 scientific publications. He received his Doctor of Medicine degree from Creighton University.