After just two years, the Moon Shots Program at The University of Texas MD Anderson Cancer Center has achieved several of its audacious initial goals, including improving the surgical outcomes in ovarian cancer patients, as well as fostering the development of new drug therapies. The program has been dedicated to advancing both molecular analysis and screening.
“Our Moon Shots Program presses on to save more lives more quickly by cultivating powerful, efficient connections between vast new scientific knowledge and our efforts to improve patient care, protect those at risk and prevent cancer outright,” said the president of MD Anderson Ron DePinho, M.D. “Moon shots gather MD Anderson’s multidimensional expertise and tap remarkable new technologies to better deploy what we already know about cancer against these diseases and to contribute creative new answers to crucial challenges.”
The main purpose of the program is to accelerate the conversion of scientific discoveries into clinical advances, as well as reduce the number of deaths caused by melanoma, lung, prostate and breast/ovarian cancers as well as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS). The co-director of the Moon Shots Program, Giulio Draetta, M.D., Ph.D., who is a professor in Molecular and Cellular Oncology, characterizes it using two concepts: “Execution and rocket science.”
“This first wave of accomplishments reflects the moon shots’ emphasis on execution. It’s a matter of more efficiently applying what we already know about cancer to help our patients,” stated Drayetta. “Rocket science enables our clinicians and scientists to make discoveries and clinical advances that really turn the world around. Achieving that will require inventions yet to come. It will take time.”
Moon Shots has been developing and utilizing innovative platforms dedicated to the study of immunotherapies, genomics, proteomics, prevention and big data, aided by MD Anderson’s Center for Co-Clinical Trials and Institute for Applied Cancer Science.
A new protocol developed through Moon Shots for determining which types of ovarian cancer should be treated with surgery upfront and need pre-surgical chemotherapy has radically increased the rate of complete surgical removal of tumors, an accomplishment that improves patient survival. One of its most prominent results is a new algorithm that allows patients to undergo less-invasive laparoscopic evaluation, which is ranked by two different surgeons to assess the cancer’s spread to other organs.
The evaluation aims to support physicians in making decisions on treatment options, and until now, patients would need exploratory surgery in order to understand the extent of the disease, as well as to remove the tumor. The procedure results in between 20 and 30% of the patients achieving “complete gross resection.” The algorithm was tested in 155 cases and revealed 89% of efficacy.
In addition, the project Making Cancer History of the Family provides genetic screening to look for mutations in the BRCA 1 and 2 genes, which are responsible for the increase of the risk for two types of cancer, a product of Moon Shot’s focus on high-grade serous ovarian cancer and triple-negative breast cancer. Inherited mutations and the possibility of risk-elevating variations are also increased, and by finding BRCA mutations, the program aims to educate family members.
Lung cancer is another one of the Moon Shots researchers’ concerns, and they have been able to identify the potential of two drugs that are currently approved for the treatment of Leukemia, as possibly also having positive results on treating lung cancer patients. This was the result of a major study, which screened 30 drugs approved by the U.S. Food and Drug Administration (FDA) on different tumors in 90 human non-small lung cancer cell lines, in order to determine which drugs can go to trial, since approved drugs transition into clinical trial more quickly.
Regarding lung cancer, the researchers have also engaged in conducting low-dose CT scans in both former and present heavy smokers, in order to increase the diagnosis of treatable, early-stage lung cancer, and reduce deaths in 20% of cases. Therefore, Moon Shots launched a local study in order to meet the needs for lung CT screening, with the main goal of identifying and validating blood and airway biomarkers, which may help in both diagnosis and treatment, as well as to study advanced imaging techniques, as well as demographic and behavioral risk factors. MD Anderson expects to be able to extend the study to a national and international level this year.
In addition, the prevention campaign also includes discouraging the use of tobacco by adolescents and helping current smokers to quit using innovative and personalized approaches. A Smoking Prevention Interactive Experience (ASPIRE) is an online anti-tobacco program, especially designed to connect local clinics to high schools in the Houston area. The program is planned to extend to middle schools as well.
For smoking cessation, innovative studies are under development to advance personalized smoking cessation techniques. Two trials will evaluate the use of genetic and neural biomarkers of reward sensitivity as indicators of treatment response. Another examines the best treatment options for people who fail to quit on either of two pharmacological smoking-cessation treatments.
Research conducted by Moon Shots also has been made progresses into chronic lymphocytic leukemia, as the investigators hope to be able to alter the standard practice of chemotherapy to new targeted therapies and immunotherapies. Among the personalized therapies developed at MD Anderson are ibrutinib and idelalisib, which were both approved by the FDA this year. Monoclonal antibody rituximab, in addition to these two and other drugs, are therapies able to induce responses in CLL patients with fewer and less harsh side effects than chemotherapy, over a long-term period.
A clinical trial including 208 CLL patients is being conducted to examine ibrutinib versus ibrutinib plus rituximab, in order to assess genomic information and understand its resistance. In addition, researchers are also examining combination therapies.
Three other first-in-human clinical trials were initiated this year to develop state-of-the art engineered immune cells, able to neutralize leukemia cells. Two of them involved T-cells based on the collection, customization, and re-infusion of the cells from umbilical cord blood, while the third focused on natural killer cells. A fourth trial is also planned this year, designed to study T cell targeting against ROR1, a protein that is found only in CLL cells.
Also in the field of drug development, two new drugs were found to be able to thwart androgen receptor-driven, castrate-resistant prostate cancer, with a clinical trial intended to find a cure for a subgroup of prostate cancer. The two drug therapies, which were already approved by the FDA, are able to target the androgen receptor-testosterone pathway differently, as well as reduce the levels of masculine hormones that influences the development of the disease.
Moon Shots engaged in preclinical studies regarding prostate cancer that investigated cell lines in mouse models as a way of finding combination treatments for metastatic castrate-resistant cancer. Therefore, they are exploring the option of combining androgen-targeting agents with drugs that hinder DNA damage repair.
In addition, a prevention-focused program was initiated as an evidence-based sun protection campaign to raise awareness about the damage that ultraviolet rays cause to children from preschool to adolescence, with special attention on the reduction of tanning bed exposure. The program comes at a time when Texas has just approved a law forbidding people under the age of 18 to use tanning beds.
The Acute Myeloid Leukemia/Myelodysplastic Syndromes Moon Shot is the part of the program dedicated to drug resistance in treating diseases, which is specially focused on hypomethylating agents. Two clinical trials have been initiated, one of the them being the first to address leukemia and a rising type of cancer immunotherapy called immune checkpoint blockade, while the other works on the toll-like receptor 2 protein (TLR2), which they believe is a potential target. They were already able to find other origins for drug resistance, by analyzing DNA, RNA, and protein activity.
The purpose of the research is to increase graft-vs-tumor response in blood stem cell transplantation, as blood stem cell may represent a cure for both of the diseases, as well as a way of eradicating transplanted immune system’s action against leukemia. The researchers believe that they will be able to replace transplantation with treatment by engineered immune T cells and natural killer cells primed to find and kill cancer cells.
“A central theme of the Moon Shots Program is to learn as much as we can from every single patient,” explained Andy Futreal, Ph.D., professor of Genomic Medicine and the program’s co-leader with Draetta. “We need to think longitudinally — how patients’ conditions, treatments and tumors change over time, and be smarter about how we collect and use that information. To do this, we need to build an engine to learn.”
Dr. Futreal is also the leader of the Adaptive Patient-Oriented and Longitudinal Learning and Optimization (APOLLO) program, which was initiated this year and focuses on leukemia. Futreal has plans to enlarge the program and also work on lung and melanoma Moon Shots.
Its purpose is creating more cohesive systems, in order to collect patients’ medical information, high-quality tissue and blood samples, and genomic and molecular analyses of those samples, in a long-term, standardized manner. The program was initiated because improving the collection, storage, access and analysis of patients’ information may determine better diagnosis and treatment, and is something “every cancer research institution on the planet is struggling with right now,” Futreal said.
“We’re sincerely grateful for those who are investing in new answers being developed by our moon shots for cancer patients and their families,” DePinho said, as the Moon Shots Program has already been able to raise $212,991,178 in grants, mainly from philanthropic work.
“Together with our industry partners, we are working to integrate and implement these technologies in practice. Our goal is to develop a better cancer care system, with the singular goal of delivering better outcomes to more patients around the world,” said Lynda Chin, M.D., chair of Genomic Medicine and leader of the Oncology Expert Advisor (OEA) system, a collaboration between the facility and IBM Watson Group. “We will be Making Cancer History.”
MD Anderson established several partnerships with global industry leaders, as a way of promoting the democratization of evidence-based care, as well as decreasing the knowledge gap by focusing on big data and social, mobile, analytics and cloud technologies. Its main partners are IBM, PwC and AT&T, however, Dr. Futreal believes that in addition to sharing cancer knowledge, “we also need to improve coordination of care and ensure continuity of care.”