Nearly everyone has been hit with the sobering news that they or a loved one have cancer. Approximately 40% of men and women will be diagnosed with cancer during their lifetime, according to the American Cancer Society. The good news is that every year, millions of Americans are defeating the disease through ongoing advancements in treatment and detection.
At Atrium Health Levine Cancer Institute and Atrium Health Levine Children’s, novel discoveries are being made every day, propelling cancer therapies forward. Philanthropy continues to provide significant funding for cancer research, including Phase I and Phase II clinical trials. Support from dedicated partners, including Swim Across America, makes this possible.
Since 1987, Swim Across America (SAA) has been “Making Waves to Fight Cancer” through its annual charity swims. The events, which take place from coast to coast, exist to raise money for doctors and researchers who are pioneers in developing new cures and treatments. With ongoing philanthropic commitments from Swim Across America – Charlotte, Levine Cancer Institute has six active research projects related to blood cancers, including:
I. Germline Predisposition to Blood Cancers
With funding from SAA, Drs. Belinda Avalos and Lawrence Druhan, along with their team in the Hematologic Oncology Translation research lab (the HOT lab), have identified novel variants in the granulocyte colony stimulating factor receptor gene (CSF3R) that increase the risk of leukemia and other blood cancers.
“Working with our collaborators at the University of Chicago, the HOT lab team has identified three new CSF3R variants that can increase the risk of the development of hematologic malignancies in carriers of these gene variants,” said Lawrence Druhan, Research Group Director at Levine Cancer Institute. “The high risk of cancer in these cases is due to altered function of the receptor protein, leading to changes in the development of white blood cells.”
Expanding on these results, the HOT lab team identified an extended family with a hereditary CSF3R variant known to cause chronic neutrophilic leukemia, a condition that carries a significant risk for the development of acute myeloid leukemia. Funding from SAA helped the team discover a candidate class of drugs for the treatment of this disorder. These findings were presented at the 63rd Annual Meeting of the American Society of Hematology in Atlanta in December 2021.¹,²
II. Personalized Medicine for Patients with CML and ALL
Tyrosine kinase inhibitors (TKIs) are commonly used to treat two forms of leukemia: chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). The current dosing strategy for TKIs is based on a “one size fits all” approach. With this method, many patients develop drug-related side effects warranting treatment discontinuation, interruption, or change, which can lead to poor outcomes. Led by Drs. Michael Grunwald, Aleksander Chojecki, Jai Patel, and Lawrence Druhan – and bolstered by SAA funding – investigators at Levine Cancer Institute have initiated an effort to determine whether there are causal relationships between the genetic differences found in each patient and the observed TKI-related side effects and toxicities.
“This study will examine how small changes in specific genes found in each individual influence drug metabolism among patients with CML and Ph+ ALL,” said Dr. Grunwald, Chief of the Leukemia division at Levine Cancer Institute. “Patient data will be used to establish associations among genetic variation, exposure, and TKI-related toxicities. Accordingly, the results from this study will begin to set the groundwork for an individualized approach to dosing TKIs, with an aim of improved compliance and decreased toxicities, ultimately resulting in better patient outcomes.”
- Trottier AM*, Druhan LJ*, Kraft IL, Lance A, Feurstein S, Helgeson M, Segal JP, Das S, Avalos BR, Godley LA. Heterozygous germ line CSF3R variants as risk alleles for development of hematologic malignancies. Blood Adv. 2020 Oct 27;4(20):5269-5284. doi: 10.1182/bloodadvances.2020002013. PMID: 33108454
- Chiad, Z, Lance, A, Seegers, SL, Paschall, SC, Drummond, K, Steuerwald, NM, Voorhees, PM, Avalos, BR, Druhan, LJ. Hereditary Chronic Neutrophilic Leukemia in a Four Generation Family Without Transformation to Acute Leukemia, 63rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) 2021.