Tracking the trajectory: An update on the Moon Shots Program
Improved surgical outcomes for ovarian cancer patients, expanded potential impact for new drugs and a novel family outreach program to head off cancers fueled by known genetic mutations are among the early innovations of MD Anderson Cancer Center’s Moon Shots Program.
First-of-a-kind combination clinical trials; advanced molecular analysis to guide treatment and screening; and a focused program to gather, store, access and apply massive amounts of information to help patients and learn along the way also are unfolding.
“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 MD Anderson President Ronald 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,” he said.
The program was launched in the fall of 2012 to accelerate the conversion of scientific discoveries into clinical advances and significantly reduce cancer deaths. The initial moon shots address melanoma, lung, prostate and breast/ovarian cancers, chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS).
Moon shots research benefits from innovative research engines in immunotherapy, genomics, proteomics, prevention and big data, as well as support by MD Anderson’s Center for Co-Clinical Trials and Institute for Applied Cancer Science.
Personalized surgery: A new algorithm has been developed to determine whether ovarian cancer patients should go to surgery upfront or have chemotherapy first. The independent assessment by two oncologists via less-invasive laparoscopy has more than doubled the rate of complete surgical removal of tumors, which is strongly associated with improved survival.
Family outreach to head off cancer: Universal screening of high-grade serous ovarian cancer and triple-negative breast cancer patients for BRCA 1 and 2 mutations allows outreach to patients’ families that includes screening for these inherited cancer-risk mutations and preventive options when appropriate.
Leukemia drugs, lung cancer targets: Researchers identified two drugs previously approved for treating leukemia that potentially hit lung cancer targets in some patients. A clinical trial of one, the targeted therapy ibrutinib, is underway for patients with treatment-resistant disease and specific mutations in the epidermal growth factor receptor (EGFR).
Better screening to catch cancer early: A study opened to address the major challenges in lung cancer CT screening — identifying who among the nation’s millions of current and former smokers should be screened and managing the high false-positive rate of CT findings. Plans are to extend the study globally in 2015.
Easing out chemotherapy: MD Anderson CLL Moon Shot experts were instrumental in the development of the targeted therapies ibrutinib and idelalisib, both approved in 2014 for CLL by the Food and Drug Administration (FDA). These and other drugs, such as the antibody rituximab, induce long-term responses with fewer and less harsh side effects than chemotherapy. Only 15% of new CLL patients at MD Anderson are treated with chemotherapy, down from 48% two years ago.
Targeting CLL with customized T cells: The moon shot opened three first-in-human clinical trials this year, deploying state-of-the art engineered immune cells designed to find and destroy leukemia cells. Two involve customized T cells, the attack cells of the adaptive immune system. One customizes a patient’s own T cells, the other transplants T cells derived from umbilical cord blood.
Intent-to-cure drug combination trial: Researchers have paired two drugs designed to thwart androgen receptor-driven, castrate-resistant prostate cancer in the first intent-to-cure clinical trial for a subgroup of prostate cancer patients. The drugs — abiraterone and enzalutamide — target the androgen receptor pathway in different ways to reduce testosterone levels. Moon shots researchers found that the combination of the drugs thwarts the resistance pathways that arise against them singly.
New combinations: Preclinical studies found specific drug combinations that include agents that target the androgen receptor pathway and agents that target the DNA damage response pathway are more effective than either treatment alone.
Presurgical targeted drug combination: Moon shot investigators launched the first clinical trial to compare presurgical treatment in combination with a targeted therapy combination to surgery alone for stage III melanoma. They’re combining dabrafenib and trametinib, FDA-approved for metastatic melanoma, as presurgical treatment to prevent recurrence. Additional clinical trials combine targeted therapy with immune checkpoint blockade drugs that unleash the immune system attack on tumors.
UV protection from preschool through adolescence: Researchers are developing an evidence-based sun protection program for preschoolers and promoting school-based efforts from kindergarten through high school. They’re also following up on successful efforts to limit tanning-bed exposure by minors.
Overcoming drug resistance: Research on resistance to hypomethylating agents, an important class of drugs used to treat these diseases, has led to two novel clinical trials. One is the first conducted in leukemia of a rising type of cancer immunotherapy called immune checkpoint blockade, blocking PD-1. Another targets the toll-like receptor 2 protein (TLR2).
Attacking with cellular immune therapies: A new project explores approaches to improve blood stem cell transplants and, ultimately, replace them with engineered immune T cells and natural killer cells.