This roundup highlights a clinical trial for a new leukemia medicine, insights into how DNA mutations are stabilized, a potential strategy for fighting leukemia, a possible biomarker predicting secondary cancer risk in patients undergoing stem cell transplant and a study linking Medicare Advantage plans with worse cancer survival.
To learn more about research at City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States with its National Medical Center ranked among the nation’s top cancer centers by U.S. News & World Report, subscribe to City of Hope Research Spotlight.
Clinical Trial Tests Potential New Treatment for Acute Myeloid Leukemia
City of Hope has opened a phase 1 clinical trial of a new potential treatment for patients with acute myeloid leukemia (AML) developed by Dr. Linda Malkas’ lab at City of Hope. The trial will test an investigational drug called AOH1996, which inhibits cancer-associated proliferating cell nuclear antigen (caPCNA), a protein that leukemia cells rely on for cell growth.
This treatment fights cancer by damaging cancer cells’ DNA and altering cell metabolism. The phase 1 trial will include patients with AML who have resisted treatment or relapsed. Patients will take AOH1996 orally twice a day continuously; those who respond could continue taking it for up to a year. After completion of the single agent phase 1 trial, a future combination study is planned to evaluate a standard-of-care regimen — Azacitidine and Venetoclax — in combination with AOH1996.
Researchers mainly will focus on evaluating the safety, side effects and dosage of the drug but will also monitor patients’ response to the drug as well as their survival. City of Hope hematologist Amanda Blackmon, D.O., is the trial’s principal investigator.
Learn more here.
A Chemical Tag That Keeps DNA From Tangling May Hold Clues to Cancer, Aging and Disease
A study by City of Hope researcher Steven Smith, Ph.D., has uncovered a new function for DNA methylation, a process that is usually thought to play a role in silencing genes by adding a chemical tag to the DNA strands. It now appears that this chemical tag stabilizes risky genetic sequences to prevent DNA damage.
Certain DNA sequences tend to slip out of place and get tangled. When this happens, the cell tries to fix the problem but often causes permanent damage that can lead to aging and cancer.
Surprisingly, previous research found that these sequences become more common as animals become more complex. One would expect that complex organisms like whales and humans would have more tangle-prone sequences than simpler organisms like mice. Yet just the opposite seemed to occur: Whales and humans appeared to have fewer of these sequences than mice. The new study helps explain why.
Dr. Smith, professor emeritus in City of Hope’s Department of Stem Cell Biology and Regenerative Medicine, found that there are two types of tangle-prone sequences. One type contains a short sequence of DNA called a CG site, which is tagged with a methylation mark. Evolution has allowed tangle-prone sequences with CG sites to become more frequent in humans because the methylation mark at the CG site helps hold DNA together, preventing it from getting tangled. The other type does not have the CG site or mark, and evolution has removed many of the sequences without CG sites since they can damage human DNA. This combination of elimination by natural selection and masking by DNA methylation prevents DNA damage by tangled DNA and extends the human lifespan by many years. In other words, the study points to new diagnostic tools and a deeper understanding of cancer, genetic diseases and aging.
Read the study in Nucleic Acids Research.
New Drug Shows Potential Against Acute Myeloid Leukemia
A study by City of Hope researchers identifies a new way to fight acute myeloid leukemia (AML), an aggressive type of blood cancer. The approach involves targeting how cancer cells make proteins, a process that is essential for the cancer’s rapid growth.
Researchers led by City of Hope systems biology professor Jianjun Chen, Ph.D., focused on a protein called FTO, which removes a chemical tag from strands of RNA. This leads to increased production of ribosomes, which act like protein factories in the cell.
Chen’s team developed a drug that destroys FTO, stopping it from removing the RNA tags, and slowing down ribosome production and cancer cell growth.
In cell and mouse studies, they found that the new investigational medicine, called FP54, was more effective than an older, similar drug. Mice treated with FP54 had fewer cancer cells in their blood and longer survival. The findings provide new insight into the role of FTO in cancer and show that FP54 could be the basis of a powerful new type of therapy.
Read the paper in Science Advances.
Potential Biomarker May Help Predict Secondary Cancer Risk in HCT Survivors
Autologous hematopoietic cell transplantation (HCT) is an effective therapy for patients with treatment-resistant lymphoma and other blood disorders, but the toxicity of treatment means some survivors develop subsequent cancers. Now, City of Hope cardiologist and researcher June-Wha Rhee, M.D., and City of Hope pediatric hematologist-oncologist Saro Armenian, D.O., M.P.H., have found a potential biomarker to identify patients at higher risk.
Researchers conducted a retrospective study of 1,931 patients who underwent HCT. They found that patients who had a condition called clonal hematopoiesis (CH) were twice as likely to develop new non-blood cancers after treatment.
Clonal hematopoiesis is a relatively common condition in older adults. It occurs when stem cells start making more and more cells with the same mutation. Around 20% of the patients in the study had CH. Researchers found that patients with more CH mutations had even greater cancer risk.
CH is already linked to many age-related diseases, and it was a known risk factor for subsequent blood cancers like leukemia after HCT. However, this is the first study to show that it is linked with non-blood cancers as well.
Read the study in the Journal of the National Cancer Institute.
Medicare Advantage Plans Linked With Lower Cancer Survival
Patients with Medicare Advantage have lower survival rates for lung and pancreatic cancer than those with traditional Medicare plans, a new City of Hope study finds.
Previous research by the team, led by City of Hope surgical oncologist Mustafa Raoof, M.D., M.S., showed that Medicare Advantage patients are less likely to have access to high-volume hospitals for certain types of cancer surgery. The new study takes a closer look at how those disparities translate to care, delivery and outcomes.
Researchers analyzed data on more than 170,000 Medicare beneficiaries undergoing treatment for lung, esophageal, gastric, pancreatic, colon and rectal cancers. Patients in both groups were equally likely to receive care that followed clinical guidelines. But enrollment in Medicare Advantage was associated with worse overall survival for all cancer types — especially lung and pancreatic cancer. Disparities were even more significant for stage 4 cancer patients.
More than half of Medicare beneficiaries nationwide are enrolled in Medicare Advantage plans, which can be more affordable. But while the plans encourage preventative care, they limit access to more specialized care through restricted provider networks and time-consuming prior authorizations.
Read the paper in Annals of Surgery.
Research Funding
Jianjun Chen, Ph.D., and Xiaolan Deng, Ph.D., received a $4.7 million grant from the National Institutes of Health/National Cancer Institute for a project entitled “Mechanism and therapeutic implication of RNA-modification-mediated codon-biased translation in acute myeloid leukemia.”
Rama Natarajan, Ph.D., and Zhen Chen, Ph.D., received a $3.6 million grant from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases for a project entitled “Chromatin remodeling factors and mechanisms in diabetic microvascular complications.”
Zhaohui Gu, Ph.D., received a $2.4 million grant from the National Institutes of Health/National Cancer Institute for a project entitled “Dissecting the Functional Role of PAX5 Mutations in B-cell Acute Lymphoblastic Leukemia.” Dr. Gu also received a $2.6 million grant from the National Institutes of Health/National Cancer Institute for a project entitled “The Role and Function of a Novel Signature Gene in BCR: ABL1 (Ph) B-cell Acute Lymphoblastic Leukemia.
# # #
About City of Hope
City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked among the nation’s top cancer centers by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.
END