MD Anderson's Moon Shots program expands into new cancer types

Originally launched in 2013, The University of Texas MD Anderson Cancer Center’s Moon Shots Program recently expanded its campaign to include six more of the most problematic cancer types.

They are B-cell lymphoma, glioblastoma, cancers caused by HPV, high-risk multiple myeloma, colorectal cancer and pancreatic cancer.

The program’s transdisciplinary team–science approach aims to accelerate the development of new treatments, diagnostic methods and prevention programs from scientific discoveries for these populations of patients with cancer.

The Moon Shots Program is fully funded by philanthropy, with nearly $300 million raised thus far.

Ronald A. DePinho

HemOnc Today asked Ronald A. DePinho, MD, president of MD Anderson, about how achieving a level of conceptual maturity and the creation of new technologies together allowed for the creation of the Moon Shots Program, as well as what additional efforts are on the horizon.

Question: How did the Moon Shots Program come about?

Answer: The program came about through the realization that we are at a true turning point in the history of cancer medicine. We were experiencing a true revolution in understanding the instigators of cancer, of the genes that were operative in forming tumors as well as maintaining tumors, understanding the biology of these genetic alterations, understanding how the immune system works and having a periodic table for genetic alterations in different cancers. These were all important conceptual breakthroughs. The other aspect was the confluence of disruptive technologies. Some shining examples of this are in sequencing capacity, where we have the ability to sequence genomes in clinically actionable timeframes. In the 1990s, it took us years and billions of dollars to sequence one genome; now, this can be done at a fraction of the cost and within days. The other major disruptive breakthrough is the ability for us to aggregate large amounts of data in a data warehouse and analyze this information using very sophisticated computational tools, most notably cognitive computing such as IBM Watson. This capability allows us to sift through and learn from the data and have this information distributed broadly to consumers and non-expert clinical providers so we can close the knowledge gap.

Q: What is the aim of the program?

A: When we examined our ability to convert our knowledge into new drugs, new diagnostics and new preventive strategies for cancer, and to translate those opportunities, it became clear to me that we were not organized to systematically deliver those clinical endpoints that matter for patients. So, we decided to launch a goal-oriented, milestone-driven program to take actionable information and convert it into prevention strategies, early-detection strategies or therapeutic strategies that would reduce cancer mortality. The goal was to conduct a flagship project in different cancers where, if knowledge was applied effectively, it would reduce cancer mortality for that cancer within the next five to 10 years of initiation of that project. The sole aim was reduction in cancer mortality. We realized there is an organizational aspect of this. Typically, academia is good at discovering, but not as good at applying knowledge and translating that knowledge into a new drug, diagnostic or public policy. This tends to be done outside of academia. However, “hand-offs” are not always perfect, so what we wanted to do was create platforms with professionals who would be responsible for execution of the discoveries. We designed a novel organizational construct where the positive attributes of academia — discovery, pursuit of knowledge and understanding of disease — could be brought together with a professional team that was responsible for moving this knowledge to results that matter for patients.

Q: What specific initiatives have come about from the Moon Shots Program?

A: During the first year that we launched this program, we went through an exercise where many groups applied and teams got together over a 6-month period to answer whether there is knowledge today that, if implemented, could reduce cancer mortality within the next 5 to 10 years. The teams went through internal and external peer review of those projects to initially nominate six different cancer types where we felt we could make an impact within the next decade. The next step within the year was to begin to assemble these large multidisciplinary teams and professional platforms and get them up and running. For the Cancer Control Platform, we hired Joxel Garcia, MD, former assistant secretary of health in the United States, as the executive director. We also created the Drug Development and Discovery Platform, which is headed by Giulio F. Draetta, MD, PhD, former head of Merck’s worldwide oncology department. During the last 2 years, we have begun to see some pretty exciting results.

Q: What type of groundbreaking research has come about as a result of the program?

A: One of our most exciting areas of research is in ovarian cancer. Mortality has not improved for ovarian cancer since the early 1990s. Essentially, what happens is patients get diagnosed at late stage and they undergo surgery and then chemotherapy. We know patients who get complete surgical resection (R0) of all visible tumor at the time of closure do very well with survival. However, if there is any residual disease, those patients do very poorly. We gathered our ovarian cancer experts and they began to question why they take the steps they do. In working together with the breast cancer experts, they decided to develop an algorithm where we first do laparoscopy on our ovarian cancer patients and then ask the question at the time of laparoscopy of whether they can achieve R0 status in the patient. If the answer is no, patients first do three rounds of systemic therapy, then comes surgery. We went from an overall 20% R0 status to an astounding 88%. There are no new drugs in this. Just the difference in sequencing with the algorithm showed a profound impact on a surrogate measure. We do not yet know if this is going to increase survival, but we do know that the main surrogate of survival is whether the patient achieved R0 status. Moreover, we now have some remarkable data in which we are able to conduct longitudinal analysis of patients with melanoma by using immune-modulating drugs. About 23% of patients who receive ipilimumab get durable responses and appear to be cured, so we asked the question: Why is it that some respond to this treatment and others do not, and can we develop strategies to more rapidly determine whether a patient will respond? We, therefore, set up a new clinical trials infrastructure within the Moon Shots Program where we do longitudinal analysis of patients with biopsies. Currently, we perform a biopsy before treatment, one after the first dose of the drug and then we do a biopsy when the disease recurs. After the first dose of treatment, we have biomarkers that can tell us whether a patient is responding to their melanoma treatment. What this means is that the patient no longer has to be subjected to additional rounds of a drug that may no longer be effective. This is really a breakthrough treatment paradigm that is going to help our patients.

Q: What is the APOLLO platform and what does it stand for?

A: To go along with our Moon Shots Program theme, we developed the APOLLO platform, which stands for Adaptive Patient-Oriented Longitudinal Learning and Optimization. This is a serial analysis of patients as opposed to the snapshot analysis we do today. Currently, we genotype patients and put them on the therapy and see if they respond. With serial analysis, we do a biopsy and molecular analysis before treatment, another analysis immediately after the start of treatment, and then, at the time of resistance, we biopsy and molecularly profile the tumor again to potentially get the patient drugs that will target those resistance mechanisms. It is a moving picture instead of a still picture.

Q: What other platforms have been created under the Moon Shots Program?

A: We have known excessive UV exposure during early childhood causes melanoma later in life. There is a period of vulnerability that children’s young melanocytes have to excessive UV exposure. Yet, children are allowed to go to a tanning salon and get radiated, and it is known that only 11 episodes of tanning bed use increases the risk for melanoma by 85%. Girls, at the age of 17, use tanning beds before a prom on average 25 times. This knowledge was in the textbooks, but it really should have been converted into the legislation that would prevent children under the age of 18 from having access to tanning beds unless medically indicated. Within the context of the Moon Shots Program, we created 10 different platforms — one being Cancer Control. This platform included experts in governmental relations whose responsibility was to work with our academicians — prevention experts, dermatologists and melanoma experts — to educate our legislature in Texas about the dangers of tanning beds. Texas became one of the first states in the United States to enact legislation that prevented kids under the age of 18 from getting access to tanning beds. In addition, MD Anderson’s Cancer Control experts went to other states and worked with stakeholders to enact similar legislation. We now have almost half of the United States with tanning bed legislation, largely as a result of our Cancer Control team’s collaborative efforts. This is an example where knowledge of disease causation has led to laws that will protect children from ever getting exposed to a carcinogen and therefore reduce the rate for melanoma development decades later.

Q: How do you see the initiative expanding in the near future?

A: We have other projects similar to the melanoma initiative. Specifically with HPV, we helped educate legislators about the effectiveness of the vaccine. We also focus on informing health care workers because there is still a tremendous amount of education needed about the opportunities for HPV vaccination. Another example is with tobacco prevention, where our goal is to increase the purchasing age of tobacco to 21. This is expected to have a dramatic impact on the number of people who use tobacco because roughly 80% of tobacco users begin during childhood. Also, within the past 2 years, we have seen the development of novel drugs that are entering into clinical trials that have significant promise and show activity in some of the most refractory cancers that exist. We are very excited about those new treatment options. We also have a number of exciting clinical trials underway. In chronic lymphocytic leukemia, for example, the vast majority of patients are receiving targeted therapy, ibrutinib (Imbruvica; Pharmacyclics, Janssen), but the ibrutinib and rituximab (Rituxan; Genentech, Biogen Idec) trial, which was driven by the Moon Shots Program, is showing very durable responses in mid-phase clinical trials. We think these findings will have a tremendous impact on the CLL population. Another project we are working on has to do with early detection of lung cancer. This will take years to do, but we are testing low-dose spiral CT and trying to develop a simple and inexpensive blood test as the first line of testing for early detection of lung cancer and to reduce the rates of false positives of spiral CT. If this works, it will have a profound impact on lung cancer mortality.

For more information:

Ronald A. DePinho, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

Disclosure: DePinho reports no relevant financial disclosures.