What Progress and Promise Does the Future Hold?
Cancer Progress Report 2015: Contents
In this section you will learn:
Research, in particular cancer genomics research, will continue to revolutionize precision medicine, including expanding the more precise use of existing therapies.
Liquid biopsies hold great promise for cancer detection, monitoring patient status, predicting patient outcomes, and changing therapeutic strategies in real time.
Research advances may eventually enable the development of precision medicines for all potential therapeutic targets.
Research has powered spectacular advances against cancer, and many more people are living longer and leading fuller lives after a cancer diagnosis than ever before. Even with this progress, it is estimated that in 2015 alone more than 1.65 million U.S. residents will receive a cancer diagnosis and more than 589,000 will die from the disease (6). Worldwide, it is predicted that in 2015 there will be 15.2 million new cases of cancer and 8.9 million deaths from this insidious disease (7). Given this enormous burden of cancer, it is clear that more research is required if we are to make future lifesaving progress.
Many researchers, however, including AACR President (2015–2016) José Baselga, MD, PhD, think that the best is yet to come, as the explosion of new knowledge about cancer and the exciting technological advances, along with our ever-increasing understanding of how to apply them, will further revolutionize cancer care.
Research in cancer genomics and its application in the clinic are the foundation of precision medicine. Cancer genomics research has dramatically increased the number of known cancer-associated genomic alterations and has thereby yielded an explosion of potential targets for the development of novel precision anticancer therapeutics. The pace of this progress is expected to not only continue, but also accelerate in the coming years, and it will be essential to engage computational biology and bioinformatics researchers more fully if we are to efficiently analyze the information and identify the targets with the most therapeutic potential (see
In addition to identifying new potential therapeutic targets, cancer genomics research may help identify markers of response to all forms of treatment (see
Retooling). This information has the potential to change patient care, because it could allow physicians to more precisely identify those patients most likely to benefit from a given treatment, including our current toolkit of anticancer agents. Moreover, those patients identified as unlikely to respond could be spared the potential harm of the treatment and immediately start an alternative treatment, saving them precious time in their race to find an effective therapy.
One area where genomics holds immense promise is in increasing the precision with which we use immunotherapeutics (see
Treatment With Immunotherapeutics), in particular immune-checkpoint inhibitors, where markers predictive of response have been challenging to identify. Two recent studies have highlighted the exciting potential of this approach, although they are early studies that need further validation before the results can be translated into the clinic. In the first study, large-scale genomics was used to identify a genetic signature of melanoma response to ipilimumab (161), whereas in the other, the presence of certain genetic mutations in colorectal cancers predicted response to pembrolizumab (162).
Despite immense progress, many tumors eventually develop resistance to current treatments and the disease progresses (see sidebar on
The Challenge of Treatment Resistance). Cancer genomics research has the potential to help physicians manage the care of patients during the course of their treatment by identifying markers that are predictive of the emergence of tumor resistance. The power of this information to transform patient care could be dramatically enhanced by pairing knowledge of genetic markers of tumor resistance with emerging technologies, sometimes called liquid biopsies.
Research has shown that during the course of cancer development and treatment, tumors routinely shed cells, lipid-encapsulated sacs called exosomes, as well as free DNA into a patient’s blood. Liquid biopsies use technological advances to capture and analyze these blood-borne tumor derivatives, including any cancer-associated genomic alterations that may be contained within them. In this way, a blood sample, rather than a biopsy of the tumor tissue itself, could be used to more easily analyze genomic alterations in a patient’s cancer. Currently, liquid biopsies are predominantly used in clinical research, but they provide great hope that physicians may soon have noninvasive ways to repeatedly sample the genome of a cancer so that they can tell quickly whether a cancer is responding to treatment or becoming treatment resistant and, if it is developing resistance, what treatment might be the most appropriate next option.
Although there are currently more than 50 FDA-approved therapeutics that target specific molecules involved in the development and progression of cancer, for other potential therapeutic targets identified by cancer genomics research or other fields of research it has proven extremely challenging to develop precision medicines with which to modify them for patient benefit. There are many reasons for this; however, there are numerous initiatives that aim to expand our understanding of these potential targets, which are sometimes referred to as undruggable, and to develop ways to overcome the challenges of developing effective therapeutics that could be used to treat the patients whose tumors harbor them. The goal of one such initiative, the RAS Initiative—launched by the NCI in 2013—is to improve treatment, diagnosis, and prevention of cancers driven by mutant RAS genes (163). Given that RAS genes are among the most frequently mutated genes in human cancers (164), including almost all pancreatic ductal adenocarcinomas (165), this initiative, if successful, has the potential to improve the lives of millions of individuals worldwide.
These are but a few examples of the extremely bright future of precision medicine.
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Progress Report 2015 Contents