In response to the White House Cancer Moonshot, the National Cancer Institute (NCI) convened a Blue Ribbon Panel (BRP) of many of the nation’s top cancer experts to give careful thought to what could be done to expedite progress against cancer. The BRP members collaborated with over 100 colleagues from across the cancer research community to identify 10 of the most compelling research opportunities poised for acceleration. In December of 2016, the 21st Century Cures Act authorized $1.8 billion in funding for the Cancer Moonshot over 7 years. In the first two fiscal years, NCI has been able to support and accelerate research in each of the 10 areas recommended by the BRP. NCI is currently planning for new research opportunities for FY 2019 and beyond. For more information about NCI’s progress and response to the Cancer Moonshot, visit: cancer.gov/moonshot.

In addition to the many initiatives that directly respond to the Blue Ribbon Panel’s recommendations, the National Cancer Institute continues to make progress in several programs that were inspired by the Cancer Moonshot.

Accelerating Therapeutics for Opportunities in Medicine (ATOM)*

The ATOM consortium is a public–private partnership whose mission is to transform drug discovery by accelerating the development of more effective therapies for patients. Welcoming new consortium members and collaborators, ATOM founding members, Frederick National Laboratory for Cancer Research, GSK, Lawrence Livermore National Laboratory, and the University of California, San Francisco, are brought together with a common aim to establish a pre-competitive, in silico drug discovery platform. This new platform, a national resource shared across the industry, will shift the emphasis from a serial design-make-test drug discovery and development process to an approach that concurrently optimizes for safety, efficacy, pharmacokinetics, and synthesizability. Working collaboratively, ATOM scientists securely combine multiple datasets, including significant data contributions from major pharmaceutical companies (with GSK being the first) as well as public datasets, to generate a new, accelerated data-driven and experimentally supported drug discovery platform that will better predict how molecules will behave in the body and achieve tumor penetration, while remaining both safe and effective.  Looking ahead, with the expectation of integration of additional pharmaceutical data and further platform developments, new and better models will be created, enabling computation to dramatically accelerate the discovery of new treatments for cancer in an integrated, model-first approach.  Additional collaboration with other pharmaceutical companies, cancer centers, government agencies, and technology companies is being sought. Read more about ATOM at https://atomscience.org.

APOLLO*

The Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) network is a collaboration among NCI, the Department of Defense (DoD), and the Department of Veterans Affairs (VA). Together, these three federal agencies are working to create the nation’s first healthcare enterprise where genetic and proteomic data will be used to inform future therapies. APOLLO utilizes the resources of these three federal agencies to create a healthcare feedback loop, called a learning healthcare system, to gain insights that translate into improved patient care. Since its inception in 2016, the APOLLO program has made progress conducting molecular characterization of samples from 8,000 patients—including veterans, active duty military personnel, and civilians—seen at the VA hospitals, the Murtha Cancer Center, and the NIH Clinical Center.

NCI Cancer Research Data Commons*

NCI Cancer Research Data Commons (CRDC) is a virtual, expandable, cloud-based infrastructure providing secure access to diverse data types and the capability to analyze those data and share or store the results. CRDC is one element of the National Cancer Data Ecosystem recommended by the Beau Biden Cancer Moonshot Blue Ribbon Panel. The NCI Cloud Resources, launched as pilots in 2016, are components of the CRDC that provide researchers access to large cancer genomics datasets co-located with elastic compute in the Google and Amazon clouds. Well over 15,000 cancer researchers have come to rely on the Cloud Resources built by Broad Institute, Institute for Systems Biology, and Seven Bridges. Through a web UI and an API, the Resources provide users access to over a petabyte of data, hundreds of analytic tools and workflows, the ability to store and share results with collaborators, and the capability to upload their own data, tools, and results – all without the need to download and host data locally.  The NCI Cloud Resources have expanded beyond the initial focus of genomics and now include proteomic and imaging data. Building upon their earlier agreements with Amazon Web Services and Microsoft, the NIH has established the STRIDES (Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability) Initiative. STRIDES launched with Google as its first industry partner and aims to reduce financial and technological barriers to accessing and computing on large biomedical data sets. Taken together, these efforts are committed to continue democratizing access to cancer research data, enabling analysis by a broad community of scientists, and advancing biomedical research and discovery.

NCI-CONNECT*

NCI-CONNECT (Comprehensive Oncology Network Evaluating Rare CNS Tumors) is a program at the National Cancer Institute (NCI), National Institutes of Health (NIH), to advance the understanding of rare adult central nervous system (CNS) cancers. NCI-CONNECT is pleased to announce that the program will offer patient consultations at no cost. In addition, if a patient is accepted on a study, treatments, tests, and other services at the NIH will also be provided at no cost. Alleviating the financial burden on patients allows them to focus on their care and treatment. Primary CNS cancers begin in the brain or spinal cord and account for less than 2% of all cancers diagnosed a year in the United States. There are over 100 different types, all of them either uncommon or rare. NCI-CONNECT is starting with 12 tumor types, each with less than 2,000 people diagnosed a year. Since these 12 tumors are rare, patients and researchers face unique challenges. Patients struggle to find expert care and treatments. Researchers struggle to identify enough patients and funds to conduct research. Enabling patients to visit the Neuro-Oncology Branch Brain Tumor Clinic at the NIH helps NCI-CONNECT address these challenges. Patients should contact [email protected] or call 240-760-6530 to make an appointment or for general questions.

The Finding Cancer Trials Collaborative*

Cancer clinical trials play a critical role for new or improved treatments to become available to patients.  To increase awareness of cancer clinical trials, and hopefully increase participation in them, NCI, in partnership with the White House Presidential Innovation Fellows (PIF) program, launched trials.cancer.gov, a streamlined website for searching for NCI-supported cancer clinical trials.  NCI is currently exploring the feasibility of improving the precision of cancer clinical search by structuring eligibility criteria. In partnership with the PIF program, NCI also developed an application programming interface (API) to make information about NCI supported cancer clinical trials more widely available.  The API enables programmers to access data from NCI’s cancer clinical trials database, the Clinical Trials Reporting Program (CTRP), and to use it in their own applications.  This provides data to the community, including advocacy groups, academia, and others in the cancer clinical trials ecosystem, so that they can build applications, search tools, and digital platforms tailored to their constituencies.  Use of the API extends the audience of cancer clinical trial information through third parties to more providers, patients, and their family members, with the ultimate goal of increasing cancer clinical trial participation. This API is also important because it’s the product of the unique collaboration between NCI and the PIF program. This is just one example of the kind of collaboration envisioned by the Cancer Moonshot, bringing together two components of the federal government to tackle solutions to critical problems.

International Cancer Proteogenome Consortium: Cancer knows no borders*

The National Cancer Institute (NCI) launched the International Cancer Proteogenome Consortium (ICPC) in 2016 due to the Cancer Moonshot, and is breaking silos through collaboration, cooperation, standardization, data sharing, and investment among the world’s leading cancer and proteogenomic research centers. ICPC institutions are united by proteogenomics, an approach that combines proteomics with genomics to allow better insights into the molecular signatures present in cancer, and today spans 12 countries and 31 institutions, with projects around 13 cancer types. Each institution has committed to the ICPC data sharing pledge and to publicly releasing data to the global research community. In addition, on September 21^st, NCI launched a new educational video that encourages the global research community to join forces and share data and knowledge that can accelerate the fight against this complex disease. ICPC commits to enabling the democratization of omics science through publicly accessible data and resources and ultimately to conduct global pan-cancer studies to better understand how cancer differs across populations and regions of the world. After all, if cancer knows no borders, why should we?

Joint Design of Advanced Computing Solutions for Cancer (JDACS4C)*

JDACS4C is a collaborative, cross-agency partnership between the National Cancer Institute (NCI) and the Department of Energy. JDACS4C was created in 2016 under the NCI Cancer Moonshot℠ to accelerate cancer research using emerging exascale-computing capabilities. The capabilities developed through this collaboration are anticipated to lead to the formulation of better risk assessment and treatments for cancer patients. Investigators from NCI and the Frederick National Laboratory for Cancer Research work collaboratively with experts in computational, data, and physical sciences from four DOE national laboratories, Argonne, Los Alamos, Lawrence Livermore, and Oak Ridge. Based on a multi-disciplinary, team science approach, the JDACS4C program has three research pilot efforts at the molecular, cellular, and population levels that align with several existing NCI and DOE program investments. With each effort jointly led by scientists from DOE national laboratories and NCI funded programs and laboratories, the pilots are each using the latest cutting-edge high-performance computing from the DOE Exascale Computing Program to accelerate progress on key cancer priorities in several areas. Looking to the future, these new capabilities and technologies will significantly reduce the time required for large-scale data analysis, simulation runs, and model development and validation. As a result, basic, translational, clinical, and population-level cancer research will accelerate dramatically helping to fulfill the Cancer Moonshot’s goal to accomplish ten years’ worth of research in five years.

Pilot 1: Predictive Modeling for Pre-Clinical Screening

The cellular level pilot, focused on developing predictive models to improve pre-clinical therapeutic drug screening, is jointly led by scientists from the NCI Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, and Argonne National Laboratory, with involvement across the JDACS4C collaboration. The goal of this pilot is to employ advanced computational technologies, including machine and deep learning, to rapidly develop, test, and validate predictive pre-clinical drug efficacy models, accelerating the rate for identifying promising new treatment options for precision oncology. This pilot is developing machine learning-based predictive models trained on experimental data from many sources, including cancer cell lines, organoids, and patient-derived xenografts (PDXs). Already, the team has established a large training database with integrated NCI data sources including the NCI ALMANAC study, the NCI Genomic Data Commons, and over a dozen additional sources, and using this integrated database, developed deep learning models for predicting tumor response to single drugs and drug combinations. Looking forward, the pilot expects to focus on the use of hybrid computational models, those employing both data and biological/mechanistic understanding, to continue to improve the initial computational models, offering the potential to improve risk identification, pre-clinical drug screening, and treatment selection when translated into the clinic.

Pilot 2: Improving Outcomes for RAS-related Cancers

The molecular level effort, which builds of the accomplishments of the ongoing NCI RAS Initiative, is co-led by scientists from the Frederick National Laboratory for Cancer Research and Lawrence Livermore National Laboratory, with involvement across the JDACS4C collaboration. The team is deepening understanding of RAS protein biology to open insights to possible new treatment options for RAS-related cancers through the integration of next generation experimental data with large scale computational simulations. Already, through leveraging computational approaches to address experimental gaps and develop multi-scale modeling and machine learning capabilities, the team has measured key experimental protein-protein and protein-membrane interactions, integrated these observations into novel multi-scale simulations to corroborate biophysics and computation on the path to develop new insights for future treatments. In the future, the ability to simulate important cancer protein interactions and cell membrane initiated signaling cascades at unprecedented scale and fidelity will be used to deepen our biological understanding of the disease while accelerating the development of drugs for RAS-driven cancers as well as other cancers associated with undruggable targets.

Pilot 3: Population Information Integration, Analysis, and Modeling for Precision Surveillance

The population level pilot, based on cancer statistics collected by the NCI Surveillance, Epidemiology, and End Results (SEER) program database, is co-led by scientists from the NCI Division of Cancer Control and Population Sciences and Oak Ridge National Laboratory, with involvement across the JDACS4C collaboration. The goal of this effort is to pilot the transformation of cancer care by applying advanced computational capabilities to population-based cancer data, leading to new understanding about the impact of new diagnostics, treatments, as well as other factors affecting patient outcomes in a real-world setting. Already the team has developed, deployed and refined pathology report annotation processes to develop critical training data and validation processes, established agreements to access real world cancer registry data, and applied the new tools to automatically extract and code key features in pathology reports. In the future, the approaches to accelerate the development of new integrated sources of health and cancer information, together with the knowledge gained from the JDACS4C molecular and cellular level pilots, are aiming to establish insights into better predicting cancer patient outcomes together with real world factors affecting patient health trajectories and clinical trial eligibility.

CANDLE (CANcer Distributed Learning Environment)

Collectively, these efforts are supported with the latest deep learning capabilities through the DOE’s Exascale Computing Project CANDLE (CANcer Distributed Learning Environment) effort. CANDLE is an open source, collaboratively developed software platform that provides deep learning methodologies and capabilities that accelerate cancer research. The CANDLE project has already delivered software for use within the scope of the JDACS4C pilots as well as other cancer research projects, conducting hands-on workshops with the cancer research community to share these important new capabilities. Future work is underway for new releases of CANDLE. Focus areas include model optimization to increase capabilities for handling even larger amounts of data with parallel computing, and development of new areas to accelerate cancer research with deep learning.

The NCI, VA Interagency Group to Accelerate Trials Enrollment (NAVIGATE)*

The NCI and VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, which launched at 12 VA (Dept. of Veterans Affairs) facilities across the country, will enhance the ability of veterans to participate in trials carried out through NCI’s National Clinical Trials Network (NCTN) and the NCI Community Oncology Research Program (NCORP). As part of the agreement, NCI will provide infrastructure funding support needed for the VA facilities to participate in NCI-sponsored trials, enhancing the ability of veterans with cancer to receive promising treatments locally. In turn, VA will manage organizational and operational activities within its national healthcare system to establish a network to focus on NCI trial goals. This program aims to overcome these challenges with dedicated staffing and a sustainable infrastructure, and to address existing barriers to trial enrollment that veterans, including minority patients, often experience. In addition, NAVIGATE will increase the participation of VA investigators in clinical cancer research, and provide opportunities for these researchers to identify studies that may be of particular importance to veterans with cancer. The program will be jointly managed by VA and NCI for up to three years. It is expected that, during this time, the participating VA sites will establish long-term capabilities to continue participation in NCI trials after this program ends. The NAVIGATE program sites will also establish best practices and share insights to help VA sites nationwide to initiate new studies and enroll more veterans in cancer clinical trials.

Partnership for Accelerating Cancer Therapies (PACT)*

As part of the Cancer Moonshot in 2016, the National Institutes of Health announced its intention to form a public-private partnership to address the need to better target promising new immunotherapies to the right patients.  In February 2018, the NIH and twelve pharmaceutical companies launched PACT, a 5-year, ~$220 million precompetitive research partnership managed by the Foundation for the NIH (FNIH), to identify and develop robust, standardized biomarkers and assays that will support selection and clinical testing of promising immune-oncology (IO) and combination therapies. PACT includes a $160 million investment by the National Cancer Institute to create Cancer Immune Monitoring and Analysis Centers (CIMACs) at four nationally recognized cancer research centers and establish a central database, the Cancer Immunologic Data Commons (CIDC), at Dana-Farber Cancer Institute.  FNIH has raised an additional $60 million from the twelve company partners in PACT to enhance this network.  Working together, the partners in PACT will develop robust, systematic, uniformly conducted clinical biomarker tests that enable researchers and clinicians to better understand mechanisms of response and resistance to IO agents.  This includes both standardizing existing biomarker assays and developing new, exploratory markers and assays so they can be used effectively in clinical trials conducted anywhere in the cancer field.  PACT is also providing scientific coordination by sharing results and information across the IO field and aligning investigative approaches to avoid duplication of effort, share resources, and enable the conduct of more relevant high-quality trials. Partners include National Institutes of Health/National Cancer Institute and U.S. Food and Drug Administration, AbbVie, Amgen, Boehringer-Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb, Celgene Corporation, Genentech (a member of the Roche Group), Gilead, GlaxoSmithKline plc, Janssen Pharmaceutical Companies of Johnson & Johnson, Novartis Institutes for Biomedical Research, Pfizer Inc, and Sanofi, FNIH and patient advocacy organizations, MD Anderson Cancer Center, Mount Sinai Medical Center, Stanford University, Dana-Farber Cancer Institute, and the Broad Institute