Precision Medicine: Where We've Been, Where We're Going

Targeted therapy and immunotherapy have drastically shifted the cancer landscape in recent years, but there is still more to accomplish in the way of precision medicine, according to the American Cancer Society’s “Blueprint for cancer research: critical gaps and opportunities.”

“Recognition that cancer is primarily a disease of the genome has fueled a recent focus on the development of more personalized or precision treatments, based largely on genomic information,” the authors of the report wrote. “Cancer treatment today may be thought of as precise choice of best options among surgery, radiation, conventional cancer chemotherapy, targeted therapy, and immunotherapy.”

Targeted Therapy

In recent decades, the FDA has approved cancer drugs that target specific molecules on cancer. These drugs, including trastuzumab (Herceptin) for breast cancer and rituximab (Rituxan) for lymphoma, offered patients more efficacious and personalized treatment options.

Despite these exciting advancements, there are still more targets to explore. The authors note that there are about 500 protein kinases encoded in the human genome, and nearly 50 protein kinase inhibitors approved for clinical use (mostly tyrosine kinase inhibitors). Others are still in preclinical testing.

“A focus of the future for kinase inhibitor development, in particular, will be on further exploration of the wealth of potential targets and continued development of tunable promiscuity, in which an individual inhibitor can target a preferred collection of kinases,” the authors wrote.

Immunotherapy

In addition to targeting cancer-related kinases, researchers have also been hard at work discovering immune targets, as, “Advances in personalized medicine have paralleled the development of cancer immunotherapies,” the researchers wrote.

Checkpoint inhibitors such as ipilimumab (Yervoy) and pembrolizumab (Keytruda) target PD-1 and PD-L1 respectively, and combining these agents with anti-CTLA-4 drugs have shown exceptional results in cancer treatment.

In the blood cancer space, CAR T-cell therapy is noted as the monumental breakthrough of the decade.

“By genetically reprogramming a patient’s T-cell receptors to recognize and bind to tumor antigens, CAR T-cell therapies have generated durable responses in patients refractory to standard-of-care treatments,” the authors wrote.

Now, patients have more treatment options than ever.

“Today, the majority of patients with cancer are treated with a combination of approaches, and the future is bright with the promise of safer and more effective combinations to treat a wide range of cancers.”

However, questions still remain, as researchers are still unsure of the clinical implications of certain mutations.

“Functional genomic analyses are required to determine whether specific genes and mutations are malignant drivers or inert passengers when they are found in particular types of cancer,” they wrote. “Furthermore, optimal profiling methodologies, the choice of timing of tumor sampling, and the effects of tumor heterogeneity remain critical issues that will affect patient management and operational efficiency in the future.”

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