HOUSTON — The University of Texas MD Anderson Cancer Center's Research Highlights provides a glimpse into recently published studies in basic, translational and clinical cancer research from MD Anderson experts. Current advances include a new combination therapy for acute myeloid leukemia (AML), a greater understanding of persistent conditions after AML remission, the discovery of a universal biomarker for exosomes, the identification of a tumor suppressor gene in hepatocellular carcinoma (HCC) and characterization of a new target to treat Clostridioides difficile (C. difficile) infections.
Utilizing combination therapy for AML
While a majority of patients with acute myeloid leukemia (AML) respond favorably to initial therapy, many will experience a subsequent relapse. Once relapse occurs, outcomes are poor and novel therapeutic options are needed. A study led by Courtney DiNardo, M.D., and Hagop Kantarjian, M.D., found that an intensive treatment regimen of fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin (FLAG-IDA) combined with the B-cell lymphoma-2 inhibitor venetoclax is effective in both relapsed/refractory and newly diagnosed patients with AML. In the study group, anticipated and manageable side effects included chemotherapy-induced cytopenias and neutropenic infections. The combination therapy produced deep remissions and helped bridge patients to successful stem cell transplants. Learn more in the Journal of Clinical Oncology.
Examining clinical outcomes of AML post-remission clonal hematopoiesis
Clonal hematopoiesis (CH) is a condition that develops when a hematopoietic stem cell, which is a stem cell that typically develops into various types of blood cells, instead makes cells that all have the same genetic mutation. CH can lead to acute myeloid leukemia (AML), and it can persist after patients are in remission. A study led by Tomoyuki Tanaka, M.D., Ph.D, Kiyomi Morita, M.D., Ph.D., and Koichi Takahashi, M.D., Ph.D., examined 164 cases of AML and found that post-remission CH occurred in around half of the patients but had little impact on their risk of relapse, their non-relapse mortality or their risk of cardiovascular disease. The findings suggest that while CH after remission from AML is resistant to treatment, it generally does not negatively affect clinical outcomes. Learn more in Blood.
Discovery of a universal biomarker for exosomes
Exosomes are virus-sized, membrane-bound particles released by all cells that are thought to carry information important for cell-cell communication. Exosomes are produced at high levels by cancer cells and contain DNA, RNA and proteins that could be useful for cancer screening, diagnostics and treatment response monitoring. A new study led by Fernanda G. Kugeratski, Ph.D., and Raghu Kalluri, M.D., Ph.D., found that exosomes contain a core proteome of approximately 1,200 proteins common to exosomes from all cells. The researchers also discovered that syntenin-1 is the most abundant protein across all exosomes, making it a potential universal marker of exosomes. Such a protein marker makes it easier to isolate and study exosomes to clarify their function and to develop approaches for using exosomes in the clinic. Learn more in Nature Cell Biology.
Immune activating tumor suppressor for treating HCC
Hepatocellular carcinoma (HCC) is the leading cause of cancer deaths worldwide, and more research is required to fully understand the biology of this disease for developing effective treatment. A research team led by Shulin Li, Ph.D., discovered WSX1 acts as an 'immune' tumor suppressor gene in HCC, effectively downregulating neoplastic PD-L1 expression in abnormal hepatocytes or HCC cells to boost immune surveillance. The suppression of PD-L1 in HCCs by WSX1 occurs through de-stabilization of a novel subtype of AKT protein. This result uncovered a novel target for cancer immunotherapies to treat HCC. Learn more in Nature Communications.
Characterizing a new target for treating C. difficile infections
Clostridioides difficile (C. difficile) is one of the leading causes of hospital-acquired infections in the U.S., and more effective therapeutic interventions are needed. The recently discovered CamA enzyme, which appears to be specific to C. difficile, catalyzes DNA methylation and is essential for spore formation and biofilm production, making it an attractive therapeutic target. A research team led by Jujun Zhou, Ph.D.; John R. Horton, Ph.D.; Xing Zhang, Ph.D.; and Xiaodong Cheng, Ph.D., performed in-depth enzymatic and structural analysis of CamA to learn how it interacts with DNA to perform its role. Their crystal structure of CamA bound to DNA provide the roadmap necessary for developing drugs to block the protein's activity. Learn more in Nature Communications.