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This is an incredibly exciting era for cancer research. Approval of novel therapeutics, coupled with an increasing public awareness of cancer prevention and early detection, has contributed to improved outcomes and dramatic reductions in mortality rates for several cancers over the past decade. Despite these advances, cancer continues to be an enormous public health challenge in the United States and worldwide (see sidebar on Cancer: A Global Challenge). In fact, it is predicted that 609,640 people in the United States will die from some type of cancer in 2018. However, many researchers, including AACR President, 2018–2019, Elizabeth M. Jaffee, MD, are extremely hopeful about the future because they are confident that research will power more advances against cancer.
One way to accelerate the pace of progress is to increase collaboration between cancer researchers and experts from other disciplines such as mathematics, physics, chemistry, engineering, and computer science. The new wave of innovations driven by convergence science will have a transformative impact on future progress across the clinical care continuum.
To achieve the full potential of precision medicine, the molecular characteristics of a patient’s cancer need to be considered along with other factors, such as the patient’s genome, epigenome, microbiome, metabolome, lifestyle, and environmental exposures, all of which are emerging as important influences on cancer initiation, development, and progression.
Integrating and harnessing data that include patient history, diagnostics, genetic tests, treatment decisions, and measured and patient-reported outcomes from large numbers of cancer patients may help answer many of cancer’s most elusive questions in real time. For example, physicians may be able to match existing FDA-approved molecularly targeted therapeutics to novel cancer types, as well as to identify subgroups of patients who are most or least likely to benefit from aggressive therapies.
Several cancer organizations as well as multi-institutional teams have already launched a number of initiatives to catalyze data integration. A few examples of these cross-institutional projects are NCI Genomic Data Commons, BRCA Exchange, ASCO CancerLinQ, Oncology Research Information Exchange Network, and AACR Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) (237).
Collection of patient-reported outcomes (PROs) enables direct measurement of the experiences of patients with cancer. Until recently, PROs have primarily been captured through surveys whereby patients fill out questionnaires to report symptoms (238-239). However, innovative methods to document PROs, captured through wearable devices or mobile apps on smartphones, are increasingly providing a critical new perspective on clinical research and patient-centered care. Detailed information about symptoms, treatment burden, quality of life, and other experiences, documented in real time, is anticipated to provide researchers with a vast amount of previously untapped “big data” that can be harnessed for patient benefit. For example, symptoms monitored in real time can alert health care professionals to problems that might require immediate attention leading to modifications in treatment or even designs of clinical trials.
The next generation of therapeutic and diagnostic technologies that are moving rapidly from the bench to the bedside has the potential to fundamentally change cancer treatment in the future.
As we accumulate large quantities of cancer patient data, artificial intelligence (AI) approaches, such as machine learning or “deep learning” programs, have the potential to help us analyze these vast amounts of health care information to derive meaningful insights we previously could not have realized. Machine learning is an application of artificial intelligence (AI) that focuses on the development of computer programs that can access and use data to learn for themselves.
A critical step in diagnosing cancer is pathology testing, which involves a pathologist’s viewing a slide on which there is a slice of the abnormal tissue, obtained through tissue biopsy or during surgery, under a conventional light microscope to determine the size, shape, and appearance of the tissue and the cells. The application of AI in pathology testing is an area of extensive research. AI has the potential to streamline processes for image interpretation from pathology slides as well as many other image sources that are routinely used in oncology, allowing for faster decision-making for people with life-threatening diseases. A digital pathology system called IntelliSite Pathology Solution, was approved by the FDA in April 2017 (highlighted in the AACR Cancer Progress Report 2017). Continued research is needed to determine the full clinical potential of AI, along with appropriate regulatory approaches to ensure safety and efficacy of these novel technologies (240-242).
Investigating the effects of changing, or editing, the genetic material of a cell is an important part of biomedical research. CRISPR is a revolutionary approach to gene editing that has emerged recently (243). It provides a faster and more precise and efficient approach to gene editing compared to previous technologies. The development of CRISPR technology was based on basic research into the immune system of certain species of bacteria. CRISPR technology is being currently used by researchers throughout the biomedical research community in numerous ways. One area of extensive investigation is to identify safe and effective ways to use CRISPR-mediated gene editing for cancer therapy (244).
A biopsy is the removal of cells or tissues from a patient for testing to help physicians diagnose a condition such as cancer or monitor how it changes in response to treatment. Traditionally, biopsies are invasive procedures. However, research has shown that during the course of cancer development and treatment, tumors routinely shed detectable cells, lipid-encapsulated sacs called exosomes, as well as free DNA into a patient’s blood (see sidebar on Moving toward Minimally Invasive Testing). Recent studies have shown that it is possible to use a blood sample, or liquid biopsy, rather than a traditional tissue biopsy, to obtain material that can be analyzed to provide information about the molecular alterations associated with a patient’s cancer (245-246). Liquid biopsies have the potential to transform early detection, diagnosis, treatment, and surveillance of cancer by identifying markers of disease, therapeutic response, resistance, and recurrence.
The human body contains trillions of microbes from many different species of bacteria, fungi, parasites, and viruses that reside in multiple sites such as the skin, eyes, mouth, digestive system, and genitals. The microbiome is defined by the NCI as the collection of all the microorganisms and viruses that live in a given environment of the human body. The gut microbiome has become an exciting new area in biomedical science, both for understanding cancer development and progression, and as a novel therapeutic modality (see Figure 18).
A potential role of the gut microbiome in cancer development has been suggested in several recent studies. For instance, the presence of certain bacterial species was reported in the guts of individuals with familial adenomatous polyposis (FAP), an inherited genetic condition that almost inevitably leads to colon cancer (see Table 3) (247). Further investigation revealed that these bacteria release toxins that can damage the DNA of colon cells, which may lead to cancer development. Future studies will examine whether early detection and manipulation of specific microbes in the gut may aid in cancer prevention or interception.
Emerging evidence suggests that the gut microbiome may also play a critical role in determining responses to cancer therapy. Certain intestinal microbes can in fact break down cancer chemotherapies, rendering them ineffective or even toxic (248-249). In addition, gut microbes can significantly influence the host immune system and potentially impact the effectiveness of cancer immunotherapies (250-251). Ongoing and future research will identify innovative approaches to harness the gut microbiome for the discovery of diagnostic and therapeutic tools in cancer.