Next Frontiers in Precision Oncology… Meet Laura Agresta, MD

Next Frontiers in Precision Oncology… Meet Laura Agresta, MD

By Administrator at 10 Sep 2020, 16:18 PM

Laura Agresta, MD
Assistant Professor, Department of Pediatrics and Human Development, Michigan State University
Fellow, Precision Cancer Therapeutics, Clinical Pharmacology and Predictive Medicine, Cincinnati Children’s Hospital Medical Center

Precision oncology aims for cures that are more effective and less toxic than conventional therapies by targeting the biological pathways that drive certain cancers. This growing field has long been a focus of Gateway for Cancer Research.

Earlier this year, Gateway and Conquer Cancer®, the ASCO Foundation presented the annual Young Investigators Award to Laura Agresta, MD, to advance her precision oncology use of genetically-informed “smart drugs” and combination therapies to treat pediatric acute myeloid leukemia (AML). The one-year $50,000 grant supports promising investigators and promotes quality research in clinical oncology.

Each year in the US, 730 children and young adults under the age of 20 are diagnosed with AML, and 67 percent survive at least five years with treatment (American Cancer Society Cancer Facts & Figures 2020). However, AML is notoriously resistant to chemotherapy and approximately 30 to 40 percent of patients will have a relapse. Long-term survival remains challenging. With the goal of improving standard of care, Dr. Agresta is leading a Phase 1 clinical trial for young patients with relapsed or refractory (treatment-resistant) AML.

AML cells resist chemotherapy by interrupting the molecular signals that would normally lead to cell death through a process called apoptosis. In recent studies, a formulation of the two most potent chemotherapies, called Vyxeos, brought about an 81 percent complete response rate in children with relapsed AML – an encouraging development. However, not all patients respond and more work needs to be done. Dr. Agresta is testing whether combining Vyxeos with venetoclax – a targeted therapy that inhibits this anti-apoptosis signaling – will improve the effectiveness of the chemotherapy.

In a recent conversation with Gateway Dr. Agresta described the promise of bringing precision oncology to care for children and young adults with cancer. Please note that comments have been slightly edited for length.

Gateway: What is the next frontier for precision oncology in children, adolescents and young adults?

Laura Agresta: Targeted therapies are by definition very specific to an individual’s cancer. Because the biology of childhood cancers is different than in adult cancers, the era of precision medicine really represents a paradigm shift in the way we think of bringing new therapies to the clinic. 

Traditionally, a new drug is studied first in adults for years, and only afterwards do we start studying it in pediatrics. While there are certainly benefits to the traditional model, true advances in precision oncology will depend largely on a willingness to fund investigations into childhood cancer biology, to develop drugs specific to childhood cancers, and to translate those drugs directly into pediatric trials.

This was done with tremendous success and efficacy for CAR-T cells engineered to kill blasts (cancer cells) in acute lymphoblastic leukemia (ALL). The CAR-T cell product Kymriah™ was investigated in and FDA-approved for pediatric patients before achieving FDA approval for adults, which represented a significant shift. I hope we can ride this wave, so to speak, and bring more childhood cancer specific therapies to the clinic in a similar way.

Gateway: What are some of the considerations in treating children with cancer and their participation in clinical trials? Why is it important to have a consortium like the Children's Oncology Group to advance research

Laura Agresta: One challenge for pediatric oncology researchers is the relative rarity of each specific type of childhood cancer. Having fewer patients with a certain cancer makes it more difficult to effectively study treatments. Since the 1950s, researchers from academic hospitals have come together to address this challenge by cooperatively sharing research and designing clinical trials in which children from all over the country – and, eventually, many countries – could participate. In 2000, these research consortia   merged to become the Children’s Oncology Group (COG). 

Through COG research, tremendous strides have been made in the treatment of childhood cancer. The most common type of childhood cancer – acute lymphoblastic leukemia (ALL) – has gone from being universally fatal to having an overall cure rate of 85 percent. COG allows us to find the best ways to integrate newly developed therapeutics – like CAR-T cells – into treatment, and the analysis of thousands of cancer tissue samples collected as part of COG research has led to critical discoveries in childhood cancer biology that has helped to identify potential cures.

Gateway: As a cancer researcher, what drives your interest and focus in pediatrics?

Laura Agresta: The resilience and curiosity of children makes caring for pediatric cancer patients endlessly rewarding. Young patients continue to adapt, learn, and grow even under the tremendous physical and emotional stress of cancer and its treatment. Practicing pediatric oncology also means I have the privilege of working with families from all backgrounds and walks of life: cancer affects children without regard for race, class, or creed.

I work with the goal of seeing our all of our young patients benefit from the kind of precision oncology research that has recently revolutionized treatments for so many cancers in adults.

Gateway congratulates Dr. Agresta on earning the meritorious Young Investigator Award, and extends sincere gratitude for her work on behalf of young cancer patients everywhere. 

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