More stories of exploration and discovery
At MD Anderson, crucial scientific knowledge gained in the laboratory is rapidly translated into clinical care. In FY17, MD Anderson invested more than $844 million in research. The institution ranks first in the number of research grants awarded by the National Cancer Institute. Here are some of the studies yielding fascinating and exciting results.
FDA grants accelerated approval of an immunotherapy drug for advanced bladder cancer
Bladder cancer patients with advanced disease have a new option for treatment after the Food and Drug Administration (FDA) approved a drug that launches an immune response against the disease.
The FDA approval of the checkpoint inhibitor nivolumab, known commercially as Opdivo, was based on a Phase II multi-center clinical trial led by Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology at MD Anderson.
“Nearly 20% of patients had their tumors shrink substantially, with some complete responses, which is a significant improvement over other second-line options for these patients,” Sharma said.
Under its breakthrough therapy designation and priority review status, the FDA granted accelerated approval of nivolumab for patients with locally advanced urothelial carcinoma whose disease progresses during or after platinum-based chemotherapy treatment, which remains frontline standard of care.
Nivolumab unleashes an immune system attack on cancer by blocking activation of a protein called PD-1 on T cells, white blood cells that find and attack abnormal cells, viruses or bacteria that have specific targets. PD-1 acts as a brake, or checkpoint, to shut down activated T cells.
The HPV vaccine’s enormous potential to stop oral cancer
Researchers have found that the human papillomavirus (HPV) vaccine may reduce the rate of oral HPV infections in young adults by as much as 88%. However, given the vaccine’s low rate of uptake in the U.S. – especially in males – the impact of the vaccine on oral HPV infections remains low.
This is the first study to explore the possible impact of HPV vaccination on oral HPV infections. Maura L. Gillison, M.D., Ph.D., professor of Thoracic/Head and Neck Medical Oncology at MD Anderson, presented the findings in advance of the American Society of Clinical Oncology’s 2017 Annual Meeting in June. The study was conducted while Gillison was at The Ohio State University Comprehensive Cancer Center.
Studies have shown HPV is responsible for several cancer types in men and women, including cancers in the back of the throat in an area known as the oropharynx. According to the Centers for Disease Control and Prevention, HPV is linked with approximately 70% of oropharyngeal cancers, and incidence of the disease is rising dramatically in the U.S.
Unfortunately, explained Gillison, no clinical trials have prospectively evaluated whether the existing FDA-approved HPV vaccines will prevent oral infections that lead to the disease. Therefore, the vaccine isn’t approved for the prevention of head and neck cancers. It is approved for the prevention of cervical, vulvar, vaginal and anal cancers in women and anal cancers in men.
The researchers analyzed data from 2011-2014 in which participants began to self-report if they had received one or more HPV vaccines. They reviewed responses from 2,627 young adults ages 18-33, and compared the prevalence of an oral HPV infection in those who received one more doses of the vaccine to those who did not.
In the cohort, the researchers evaluated the prevalence of HPV type 16, 8, 6 and 11 – the four types included in HPV vaccines before 2016.
They found that the prevalence of vaccine-type infections was far less common in individuals who had been vaccinated than not vaccinated. When comparing the two groups, the infection rates in the vaccinated group was about 88% lower than in those who hadn’t been vaccinated.
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 deadliest – only 10% of patients surviving five years. 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.”
photo by Adolfo Chavez III
Nivolumab plus chemotherapy improves leukemia patients’ survival
Combining the immunotherapy drug nivolumab with standard chemotherapy more than doubled response rates and improved overall survival in patients with acute myeloid leukemia (AML), according to MD Anderson researchers.
The results were from a Phase IB/II ongoing study that paired nivolumab with azacitidine (AZA) in patients who had previously demonstrated poor complete response and overall survival.
“The combination of AZA and nivolumab showed a response rate of 34 percent, which compares favorably to a historic response rate of 12 to 15 percent with AZA alone,” says Naval Daver, M.D., assistant professor of Leukemia.
The study, which followed 51 patients with an average age of 69, showed median overall survival for those treated with combination was 9.3 months, compared with an historic median of 4.7 months for patients treated with AZA alone.
Daver says longer follow-up is necessary to confirm the overall survival benefit of the approach.
Predicting a deadly leukemia that strikes after cancer treatment
Patients who’ve been successfully treated for breast, colon and other cancers can go on to develop an often-fatal form of leukemia, sometimes years after completion of treatment, due to a genetic mutation leading to secondary malignancies known as therapy-related myeloid neoplasms (t-MNs).
A study led by Andy Futreal, Ph.D., chair of Genomic Medicine, and Koichi Takahashi, M.D., assistant professor of Leukemia and Genomic Medicine, revealed pre-leukemic mutations, called clonal hematopoiesis, may predict whether patients develop t-MNs. Clonal hematopoiesis appears to function as a biomarker for patients who develop t-MNs, a leukemia recognized for its extremely poor prognosis.
Being able to detect t-MNs earlier is crucial given that the disease usually occurs three to eight years following chemotherapy and/ or radiation therapy.
Futreal’s team studied 14 patients with t-MNs and found traces of pre-leukemic mutations or clonal hematopoiesis in 10. To determine if pre-leukemic mutations could reliably predict whether the patients would develop leukemia, the researchers compared prevalence of pre-leukemic mutations in the 14 patients with 54 patients who did not develop t-MNs after therapy.
“We found that prevalence of pre-leukemic mutations was significantly higher in patients who developed t-MNs (71%) versus those who did not (26%),” says Futreal. “Based on these findings, we believe pre-leukemic mutations may function as a new biomarker that would predict t-MNs development.”
CAR-equipped natural killer cells target blood cancers
Immune cells with a general knack for recognizing and killing many types of infected or abnormal cells also can be engineered to hunt down cells with specific targets on them to treat cancer, researchers at MD Anderson reported in the journal Leukemia.
The team’s preclinical research shows that natural killer (NK) cells derived from donated umbilical cords can be modified to seek and destroy some types of leukemia and lymphoma. Genetic engineering also boosts the NK cells’ persistence and embeds a suicide gene that allows the modified cells to be shut down if they cause a severe inflammatory response.
A first-in-human Phase I/II clinical trial of these cord-blood-derived, chimeric antigen receptor-equipped natural killer cells opened at MD Anderson in June for patients with relapsed or resistant chronic lymphocytic leukemia acute lymphocytic leukemia, or non-Hodgkin lymphoma. All are cancers of the B cells, another white blood cell involved in immune response.
The chimeric antigen receptor (CAR) - so-called because it’s added to the cells - targets CD19, a surface protein found on B cells.
MD Anderson’s Moon Shots Program™ funds the clinical trial, which is led by Katy Rezvani, M.D., Ph.D., and Elizabeth Shpall, M.D., both professors of Stem Cell Transplantation and Cell Therapy.
