Cancer early detection research is poised to transform patient survival, but significant hurdles stand in the way of translating new findings into clinical application, leaders of the field assert in the journal Science. They detail the key challenges and chart a clear path to overcome them.
Early detection aims to identify signals of dangerous cancers or precancerous changes at the earliest time point, when treatments stand the best chance of improving survival and limiting harm. As it stands, roughly half of all cancers are diagnosed at an advanced stage.
Figure: Patients survive longer when cancer is detected at an early stage (Crosby et al., Science).“Late-stage detection of cancer is a global problem that is exacerbated in resource poor settings, demonstrating that equity is a considerable challenge,” the authors observe. “Patients diagnosed with later-stage cancer can miss the window for curative intervention, and expensive later-stage systemic treatments are often associated with severe side effects and worse outcomes.”
The authors include OHSU’s Lisa Coussens, Ph.D., and Sadik Esener, Ph.D. Coussens is professor and chair of the Department of Cell, Developmental and Cancer Biology in the OHSU School of Medicine, and associate director for basic science in the Knight Cancer Institute. Esener is professor of biomendical engineering and director of CEDAR, the Cancer Early Detection Advanced Research Center at the Knight Cancer Institute.
At CEDAR, Knight Cancer Institute scientists are probing cancer’s initiating events and early premalignant changes, and applying this knowledge to develop low-cost screening tests, determine which early cancers to vigorously treat, and direct precision therapies to minimize drug toxicity.
‘we are at the tipping point for early cancer detection research’
Powerful technologies are blooming and opening many paths forward. Researchers are now able to glean significant information from the cells, nucleic acids and proteins released by early tumors and surrounding tissue abnormalities accompanying the early malignant process.
“With the ever-increasing depth of biological insight and pace of technological innovation, we are at the tipping point for early cancer detection research and its translation to the ultimate objective of early curative interventions and increased cancer survival,” the authors note.
The challenges they identify fall into five broad categories:
- Understanding the biology of early cancer: What should we look for, and, once found, how can we know which early lesions will progress to become aggressive, consequential disease versus indolent, inconsequential disease that would not threaten survival?
- Determining risk: There are substantial challenges in knowing which populations or individuals are at greater risk of developing cancer and therefore in deciding who should be tested and how tests should be interpreted and acted on.
- Finding and validating biomarkers: Early tumors are miniscule—discovering sensitive markers of their presence and robustly validating them presents an archetypal needle-in-a-haystack challenge.
- Developing accurate technologies: there is a considerable challenge in developing technologies that are sensitive enough to detect markers of early cancers and specific enough to avoid false alarms or overtreatment for inconsequential disease.
- Evaluating early detection approaches appropriately: The ultimate challenge is to robustly demonstrate that a new early detection approach can indeed detect cancers early and ultimately save lives. The relative scarcity of cancer in the general population can make this a difficult, prolonged, and extremely expensive process.
Considering the potential benefits of early detection, the authors state that the proportion of cancer research funding dedicated to early detection remains disproportionately low:
More must be done, particularly in supporting validation of markers and tests. Dedicated funding would also help attract early career researchers to the field and enable them to become established. The relatively long timelines of early detection research and test development necessitate a rethink about traditional fellowship and grant models of supporting and evaluating early career researchers to incentivize them to establish a career in this field.
While the pharmaceutical industry has invested proportionally little in early detection compared with drug development for later-stage cancers, the authors say there appears to be increasing interest among investors and large corporations. They see a growing realization that early detection will change the business model for cancer treatment.
Early detection of cancer by David Crosby, Sangeeta Bhatia, Kevin M. Brindle, Lisa M. Coussens, Caroline Dive, Mark Emberton, Sadik Esener, Rebecca C. Fitzgerald, Sanjiv S. Gambhir, Peter Kuhn, Timothy R. Rebbeck and Shankar Balasubramanian. Science (March 18, 2022)
Highlights from the Fifth Early Detection of Cancer Conference by Joe Rojas-Burke. Cancer Translated (March 25, 2021)