MD Anderson cancer experts share discoveries at AACR Annual Meeting
MD Anderson staff
A number of MD Anderson physicians and scientists chaired or co-chaired sessions and presented research, ranging from racial disparities in the quality of life of minority colorectal cancer patients to a potential druggable target for prostate cancer, at the American Association of Cancer Research Annual Meeting earlier this month in Washington, D.C.
In addition, Gordon Mills, M.D., Ph.D., chair of Systems Biology, was elected to the AACR Board of Directors, and Stanley Hamilton, M.D., head of Pathology and Laboratory Medicine, was named a Team Science Award Winner.
Here’s a look at some of the research presented by MD Anderson:
Immunotherapy combo shows promise for kidney cancer
Immunologic changes observed in an early study of patients with metastatic renal cell carcinoma (MRCC) raised the possibility for a larger clinical study of combination immunotherapy, according to findings reported by MD Anderson researchers.
The results of an open-label pilot study comparing combinations of anti-PD1 (nivolumab) alone, or in combination with either anti-CTLA-4 (ipilimumab) or anti-VEGF (bevacizumab) therapies, revealed “promising clinical activities” in patients with metastatic renal cell carcinoma (MRCC).
In this study of 60 patients, 44 were “evaluable” for clinical responses for at least 12 weeks. The combination of nivolumab plus bevacizumab, a drug that inhibits tumor blood vessel formation, appeared to result in the highest response rate in the study, with 53% (10 of 19) of patients experiencing either a complete or partial response. This group also reported higher levels of adverse effects, mostly due to bevacizumab-related hypertension, which can be controlled by standard medications.
“This trial was aimed at getting pre- and post- treatment samples to evaluate immune responses in patients in order to understand potential mechanisms of response and resistance that may be common or unique,” said Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology. “Immune and molecular correlative studies may allow us to identify novel biomarkers that can be used for correlation with clinical outcomes in MRCC patients.”
Read more about the study in the MD Anderson Newsroom.
Minority colorectal cancer patients report
higher burden of poor quality-of-life
A study of racial disparities in health-related quality of life of colorectal cancer patients revealed that, compared to white patients, Hispanics and blacks had a higher burden of poor health-related quality of life (HR-QoL), which resulted in shorter median survival. However, Hispanics had a longer average survival time — 85.4 months — compared to blacks at 47.8 months and whites at 43.2 months.
The study, which surveyed 450 white, 366 Hispanic and 316 black patients, was led by Michelle Hildebrandt, Ph.D., assistant professor of Epidemiology, and followed up on a prior MD Anderson survey that observed lower HR-QoL scores among minority colorectal patients compared to whites. The research looked more closely at predictors of HR-QoL by racial group and how these differences were linked to colorectal cancer survival.
“In this study, we focused on identification of patterns of racial disparities in health-related quality of life scores and relationship to differences in prognosis,” said Hildebrandt. “White, Hispanic and black colorectal cancer patients within one year of diagnosis at MD Anderson completed a quality of life questionnaire to determine mental and physical aspects of quality of life.”
Hildebrandt employed the Short-Form-12 survey (SF-12), a commonly used tool to measure patient outcomes, with 12 questions designed to assess functional health or Physical Composite Summary (PCS) and mental well-being or Mental Composite Summary (MCS). Patients also completed a questionnaire to collect epidemiology and socio-demographic variables. Vital status and histology information was obtained from MD Anderson’s tumor registry.
In the SF-12, the “norm” is set at 50 so anything below 50 is considered a poor
quality of life compared to the general population.
Read more about this study and its findings in the MD Anderson Newsroom.
Protein identified as potential druggable
target for pancreatic cancer
A protein known as arginine methyltransferase 1 (PRMT1) may be a potential therapeutic target for pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, and one of the most deadliest with a less than 10%, five-year survival rate. PRMT1 is involved in a number of genetic processes including gene transcription, DNA repair and signaling.
“Our study has identified and validated for the first time an arginine methyltransferase as a novel genetic vulnerability in PDAC,” said Giulio
Draetta, M.D., Ph.D., professor of Genomic Medicine and director of Institute for Applied Cancer Science (IACS). “These findings strongly suggest a role for PRMT1 in PDAC development and illuminate a path toward the development of therapies for patients in desperate need of innovative solutions.”
Various treatment regimens have failed to improve PDAC patient survival, driving the critical need for finding druggable targets essential for tumor maintenance. Draetta’s team developed an in vivo platform called Patient-based In vivo Lethality to Optimize Treatment (PILOT), a technology enabling systemic identification of tumor vulnerabilities in patient-derived tumors. Through PILOT, they discovered novel epigenetic drivers in PDAC, including PRMT1 in tumors that harbor KRAS mutations on the background of p53. KRAS and p53 are genes often associated with cancer.
“Through this assessment of epigenetic regulators, we identified PRMT1 as a top scoring ‘hit’ in these patient-derived tumors,” said Virginia Giuliani, Ph.D., a senior research scientist at IACS. “This novel dependency was subsequently validated in multiple patient-derived pancreas models.”
The team confirmed that genetic “knockdown” of PRMT1 significantly impaired PDAC cell growth in vitro through use of genetic editing tools, including CRISPR and small hairpin RNA (shRNA). This correlated with a global reduction in arginine methylation, which controls multiple cellular processes, including DNA replication and DNA repair.
Read more about the research in the MD Anderson Newsroom.
Stand Up to Cancer innovation grant
funds microbiome study
An Innovative Research Grant from Stand Up to Cancer will help an MD Anderson physician-scientist and her team understand how the bacteria in the digestive tracts of melanoma patients affects their response to a common immunotherapy drug.
The $750,000, three-year grant to Jennifer Wargo, M.D., associate professor of
Surgical Oncology and Genomic Medicine, was announced at the annual meeting of the American Association for Cancer Research.
“We have encouraging preliminary evidence from a clinical study that the diversity and composition of a patient’s gut microbiome may play a significant role in determining how they respond to immune checkpoint blockade – specifically anti-PD-1 therapy,” Wargo said.
“This Innovative Research Grant will help us address two important questions: exactly how gut microbes influence the immune system and how we might manipulate that to improve treatment,” said Wargo, who also co-leads the Melanoma Moon Shot™, part of MD Anderson’s Moon Shots Program™ to reduce cancer deaths by accelerating development of therapies from scientific discoveries.