Cancer Moonshot 2020: Next Generation Standard of Care for Cancer

My mother died of metastatic breast cancer. Over the past two decades, death rates associated with cancer have steadily declined. However, cancer is still the #2 cause of death for the entire US and the #1 cause of death in 21 states.¹ Although overall mortality rates are decreasing, deaths related to specific cancers - hepatic and pancreatic - are rising. These data suggest that there is far more work to be done to win the war on cancer.

My mother fought breast cancer for over a decade using the standard treatments of chemotherapy, surgery and radiation. After treatment, the cancer would go into remission for a few years and then reoccur in another part of her body requiring the same procedure - chemotherapy, surgery and radiation. Chemotherapy was especially taxing on her body. She experienced hair loss, extreme fatigue, and nausea. Over time she sustained significant weight loss, cognitive and neural dysfunction. The impact on her quality of life was enormous. Moreover, the process of determining the correct chemotherapeutic to treat her disease was exhausting. In several instances, one chemotherapeutic that successfully managed her disease early on was shown to be ineffective after she relapsed. Therefore, the oncologist tested a series of drugs to find an appropriate agent to control the growth of the tumor. In the process, her body began to slowly break down. She could no longer work and needed around the clock care.

Why is chemotherapy so destructive to the body?

Chemotherapies are small molecules that disrupt the machinery that allows cells to divide. In general, tumor cells proliferate rapidly. Therefore, they are sensitive to chemotherapeutic agents. The conundrum is that there are rapidly proliferating normal cells that have very important functions for the body e.g. stem cells in the bone marrow that make blood. Using chemotherapeutics as a strategy to kill cancer cells is like using a bomb to fight terrorist living amongst innocent civilians. As you can imagine, this strategy produces immense collateral damage.

Why do chemotherapies fail?

Fundamentally cancer is thought to be directly related to mutations or changes in the DNA causing cells to transform from normal to malignant. Malignant cells tend to have increased mutations rates that confer survival advantages. Similar to bacteria that acquire resistance to antibiotics, malignant cells can acquire resistance to chemotherapeutics via mutations that render the drug ineffective. Alternatively, tumors may contain subpopulations of cells that are innately resistant to an agent. After treatment, one population dies and later the resistant subpopulation grows.² Understanding how gene mutations in tumors influence their susceptibility to different chemotherapeutics is an area of much interest and research.

What is a potential solution?

Dr. Patrick Soon-Shiong, physician scientist and founder of NantWorks, launched an initiative called Cancer Moonshot 2020, to usher in the next generation standard of care for cancer treatment. This treatment will include the following:

• Diagnostic genomic sequencing for each patient’s cancer. Cancer is a heterogeneous disease, meaning that one patient’s luminal A breast cancer may not be equal to another patient’s luminal A breast cancer. Rather than treating these diseases as the same condition, Cancer Moonshot 2020 proposes that we perform a “reconnaissance mission” or gather Intelligence on the enemy then design a bullet with each individual cancer cells name on it. Dr. Soon-Shiong developed a molecular test called GPS cancer (Genomic Proteomic Spectrometry Cancer) to identify mutations and measure changes in gene products. This molecular “fingerprint” provides clinicians with invaluable information for designing individualized cancer treatments.

• Novel combinations of targeted therapies including cell-based immunotherapy (dendritic cells, natural killer cells and T-cells), immunomodulators, genetically-engineered adenoviral based tumor vaccines, metronomic chemotherapy and low dose radiotherapy designed to treat a patient’s unique tumor “signature”. The next step is to implement therapeutics that specifically home in on malignant cells and destroy them while leaving normal cells unharmed. Immunotherapy utilizes the precise specificity of immune cells to perform a “search and destroy” mission aimed specifically at an individual patient’s tumor cells.

• Novel technology that generates evidence based treatment algorithms for patients by integrating clinical data and molecular diagnostics. NantHealth has developed a technology platform (NantOS) that enables investigators to upload diverse data sources such as electronic medical records, vital signs, labs, pharmacy and genomic data. This data is analyzed against their proprietary knowledge platform resulting in an optimized treatment algorithm. The software will access 13,000 active clinical trials and over 2500 evidence based protocols to assist investigators in determining the most effective treatment/investigative trial for their patient.

Under the umbrella of Cancer Moonshot 2020 the National Immunotherapy Coalition (NIC) has made over 60 investigative and FDA approved biological agents available for combination therapy. A number of phase II protocols are yielding promising results. By 2020 Cancer Moonshot will screen 100,000 patients, randomize 20,000 patients with 20 tumor types in various stages of disease.³ This effort may completely transform the cancer journey as experienced by the clinicians, the patient and their families.

How may this impact research sites?

A prospective subject comes into the site for pre-screening. Following consent, the subject’s demographics and medical history are collected and/or confirmed against the electronic medical records shared using the NantHealth system. Study coordinators will collect vital signs and ECGs using the DeviceConX software that captures the information directly from the machine and sends it to the electronic medical record on the Nant system. Similarly, results from labs, Imaging data and GPS sequencing will be sent directly to the eMR to be processed by software in the NantOS system. The data will be analyzed, the PI and staff will review the generated profile with decision tree for treatment, then decide which clinical trial the subject is most likely to benefit from. The technology streamlining logistics at the site combined with new molecular diagnostics, biomedical data and improved therapeutics may reduce cost and improve treatment outcomes.

How does my site get involved in this effort? Sites that desire to get involve can contact Carla Balch at carla.balch@nantcare.com to apply for membership to the Quality Cancer Care alliance (QCCA). The QCCA is an organization of oncology practices committed to providing their cancer patients access to the most current novel therapies based on their individual tumor signatures.

Denise Michelle Davis, Ph.D. is a Clinical Research Associate, CRA I for QuintilesIMS

References

1. CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. doi: 10.3322/caac.21332. Epub 2016 Jan 7.
2. Med Princ Prac.2005;14(suppl 1):35–48DOI: 10.1159/000086183
3. www.cancermoonshot2020.org