CPRIT Funds Cancer Research

With a community-led approach to improve access to cancer-related preventive services through Legacy Community Health, an FHQC, in collaboration with the Houston Methodist Neal Cancer Center and the Texas A&M Health Science Center, Esnaola and his collaborators hope to make substantial contributions to screening, early detection and reduction of mortality rates for breast, cervical, colorectal and liver cancers, as well as for hepatitis C. “The CPRIT project will create a link between the community and clinical providers to make cancer-related preventive services available via three Legacy Community Health FHQCs to patients in the Greater Fifth Ward Lyons, Santa Clara and San Jacinto/Baytown over three years,” said Esnaola, who is also Division Chief of Surgical Oncology and Gastrointestinal Surgery at Houston Methodist. “The grant will also make collaboration possible with The Rose, enabling them to extend breast cancer mobile screening services to all three Legacy locations.” This grant made the proposed program possible. It leverages well-established partnerships and incorporates dissemination and implementation of evidence-based cancer education, screening and early detection, as well as culturally appropriate education and patient navigation. Qing Yi, MD, PhD, Director of the Center for Translational Research in Hematological Malignancies at Houston Methodist, received an academic research award for individual investigator research for clinical translation (RP240075) $1,921,388 for “Combination Therapy Using ATRA and Carfilzomib to Treat Proteasome Inhibitor Refractory Multiple Myeloma.”

Yi’s research will focus on multiple myeloma—a bone cancer characterized by the accumulation of tumor cells in the bone marrow. Myeloma remains incurable despite the many chemotherapy drugs available. Patients often become resistant to myeloma treatments, including traditional chemotherapeutics and novel agents. Additionally, some patients exhibit initial resistance, not responding to chemotherapy at all. Those who do respond often experience relapse after treatment and succumb to the disease. “Proteasome inhibitors, such as bortezomib and carfilzomib, have good therapeutic efficacy for multiple myeloma, yet their initial response rate in myeloma patients is only 27- 48%,” said Yi, who is also Associate Director of the Cancer Center Basic Research Program in the Dr. Mary and Ron Neal Cancer Center. “Even patients with a robust initial response to the drugs become resistant when treated again after relapse.”

To overcome resistance and advance the development of more effective therapies, Yi’s team did a high-throughput screening of 1,855 FDA-approved drugs and found that a treatment used for patients with acute promyelocytic leukemia—all-trans retinoic acid (ATRA)—can overcome human multiple myeloma cell resistance to the current standard-of-care drugs. ATRA alone does not kill myeloma cells; it enhances human myeloma cell sensitivity to bortezomib and carfilzomib. Yi believes that ATRA may be used to treat patients with myeloma to restore their response to these drugs. The CPRIT grant will be used to conduct a first-in-human phase IB/II clinical trial to determine the safety, tolerability, efficacy and recommended phase II dosing of ATRA/carfilzomib combination therapy to treat proteasome inhibitor resistance in multiple myeloma patients. Esnaola and Yi both joined Houston Methodist as CPRIT recruits in 2018.