Deep knowledge of immunology, cancer biology, and disruptive technology in computational science and molecular profiling has positioned us to dethrone the emperor of all maladies. The cancer research community is prepared to fulfill President Barack Obama’s call for a national cancer moonshot aimed at eradicating cancer. Elevating cancer to a national priority has given hope to patients and families impacted by this deadly disease. This is an opportune time to act decisively.
In 2012, The University of Texas MD Anderson Cancer Center reinforced its commitment to accelerate progress in cancer with the launch of our Moon Shots Program, a massive multidisciplinary goal-oriented effort designed to more rapidly convert scientific discoveries into lifesaving advances through the integration of academic discovery and industry-like execution. Buoyed by the influx of more than $500 million dollars from diverse sources, nearly 2,000 faculty and staff have adopted a novel translational paradigm, which has already begun to yield results in cancer prevention and treatment more rapidly than we anticipated.
Bringing Together Multidisciplinary Teams With Clear Goals
Our progress derives from the establishment of “platforms” focused on execution, which bring together multidisciplinary teams of academic scholars and those with diverse expertise focused solely on developing, implementing, and achieving project goals in a milestone-driven, accountable manner. There are 10 such platforms, spanning cancer control efforts in policy and education to drug development to longitudinal genomic/proteomic/immune profiling to the use of big data and cognitive analytics. These execution-oriented professional platforms with dedicated experts are transforming the ability of our academic researchers to convert knowledge into clinical endpoints.
One illustrative example of the value of our platforms is in the care of our youngest patients. Although much progress has been made since the 1950s in raising the survival rates in childhood cancers from just 10% to nearly 80% today, many children still die of cancer. To accelerate the declines in cancer mortality, we harnessed the capability of three Moon Shots platforms, including the Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) platform.
Defining the Evolving Spectrum of Genomic and Immune Alterations in Cancer
In this project, our multidisciplinary teams of clinicians, researchers, and computational scientists seek to define the spectrum of genomic alterations in young sarcoma patients with progressive disease following a period of response or with nonresponsive disease to initial first-line treatment. By performing deep sequencing at the whole genome, exome, and transcriptomic levels as well as immune profiling in pretreatment, relapse, and refractory cases, we seek to gather insights into the genomic and biologic evolution of treatment-resistant cancers, which may inform the application of existing drugs or development of new drugs. This longitudinal approach stands in contrast to the more traditional precision medicine model of taking a diagnostic sample as a fixed point of knowledge about the genomic and immune characteristics of a patient’s tumor, which may change radically over time as a result of disease evolution, genomic and cellular plasticity, and treatment pressures.
Our approach allows several important comparisons to be made ¬immediately:
- Are there aggregate differences between the molecular genomics of relapsed/refractory disease, and are they seen in large-scale cancer genomics on primarily ¬diagnostic samples?
- Can these efforts identify potential markers of inherently more aggressive disease?
- Are there similarities or differences between the biology implicated in relapsed and primary refractory disease? Is there insight into resistance mechanisms?
- Can new targets/pathways that emerge from the combined interrogation of the mutation, expression, and immune profile data sets yield opportunities for therapy?
Learning From Every Patient
In patients enrolled for primary treatment, 40% are expected to relapse within 5 years. When relapse occurs, the tumor tissue collected at primary treatment and relapse will be compared to determine how the genome has evolved, both in terms of new mutations and changes in the architecture of existing ones. Immune cells will also be catalogued. With this new paradigm of longitudinal sampling and analyses supported by the APOLLO platform, progressive changes specific to an individual’s cancer, from diagnosis to relapse or metastasis, will be identified and provide a highly detailed portrait of the molecular and immune profile changes over time and because of therapy.
Another of our platforms offers advanced clinical and research data aggregation and analytics to enable precision medicine for every patient. This “big data” approach will revolutionize our ability to learn from each patient and dramatically accelerate translational research to a new level. It will also enable teams of clinicians, laboratory scientists, and computational scientists to rapidly explore hypotheses and derive new insights from unbiased analyses of the data.
Together with the APOLLO platform, physicians will be able to find answers to such questions as why some patients never respond to treatment; why some patients initially respond and then relapse; and why some patients have long-lasting responses. The end goal is to improve outcomes and reduce suffering worldwide by driving the development of new standards of care for these patients. To facilitate the efficient and rapid transfer of this new knowledge to physicians everywhere, we are developing the Oncology Expert Advisor, powered by IBM Watson, which will provide decision support to practicing oncologists based on the latest advances in cancer.
Forging a New Frontier
Great progress has been made against pediatric and adult cancers, but our fight is far from over. Harnessing the power of data derived from dynamic longitudinal profiling will allow researchers to explore new frontiers, find more effective targeted treatments, and give our most vulnerable patients the opportunity to live long and productive lives.
Launching a national moonshot initiative to accelerate progress is no simple feat, but past generations have taught us that if we put our minds and will to this goal, we can and will succeed. Future generations are counting on us to seize this historic opportunity and fulfill our solemn responsibility. On behalf of our patients and families, we thank President Obama and Vice President Joseph Biden for their support and leadership in initiating this national effort to end cancer.
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