rizona Sen. John McCain’s recent diagnosis of the hard-to-treat cancer glioblastoma stands in contrast to recent media reports that paint an optimistic picture of cancer treatment in America. A sampling of headlines includes “Cancer survival rates at all-time high” and “Cancer death rates continue to decrease in the United States.”
Driving much of the progress are emerging advances in three vital areas: cancer prevention and early detection, immunotherapy, and precision medicine approaches that match patients to targeted therapies. These developments are yielding benefits for nearly every site- or tissue-specific cancer, in at least some of their subtypes. But what about those cancers that aren’t playing by the same rules?
“Common cancers, including pancreatic, brain, and lung, remain stubbornly difficult to treat. … Aggressive cancers such as these are difficult to diagnose early and lack adequate treatment options,” the American Society for Clinical Oncology said in its 2017 “State of Cancer Care in America” report.
Those cancers present a counter-narrative to the idea that we are well on our way toward eradicating cancer as we know it. Brain cancer, in particular, offers a window into intractable cancers. Its most common — and most lethal — form is called glioblastoma multiforme (GBM). Paradoxically, it is one of the most molecularly and genetically characterized of all tumors, having been selected a decade ago for a pilot project as part of The Cancer Genome Atlas.
Data from that work on glioblastoma, and subsequent research enabled by it, created a veritable treasure trove of biological information on this cancer that led to numerous potential targets for new therapies. Yet hundreds of studies testing many of the latest and greatest cancer drugs and treatment modalities have not produced durable results or improved overall survival in people with glioblastoma. This includes recent setbacks with checkpoint inhibitors, vaccine-based immunotherapies, and precision small-molecule inhibitors, all of which have been making significant differences in certain cancers of the breast, colon, lung, kidney, bladder, liver, head, neck, blood, and skin.
Nearly half of all cancers could be prevented, and many more are caught early through improving screening guidelines. Sadly, that doesn’t apply to brain cancers. And while most cancers typically become deadly only once they’ve spread to other parts of the body, glioblastoma is deadly despite rarely moving outside the central nervous system.
What can we do about a cancer that defies all the norms? Additional resources are always welcome, of course, but perhaps even more essential is a recalibration of how we approach complex and aggressive malignancies.
We must recommit to rigorous but “basic” biological research. What we’ve learned from the many failed trials for brain cancers is that they are a highly complex and adaptable foe, adept at evading treatments of all classes. We need to understand why previously tested drugs didn’t work in patients with glioblastoma, as well as identify why it and other brain cancers are so resistant to therapy. A key element of this treatment resistance is the blood-brain barrier, the tight cellular network within the brain’s small blood vessels that protect the organ from toxins and chemicals. Most cancer drugs haven’t been designed to cross the blood-brain barrier. Without that ability, promising drugs can either fail to reach the tumor or hit their target with inadequate doses.
The Defeat GBM Research Collaborative is taking a meticulous approach to identify targets for therapy along with potential mechanisms of resistance. This kind of approach is needed to move the field beyond the simplistic tactic of repurposing — sequencing individuals with glioblastoma and trying to match them to treatments developed for similar mutations in other cancers.
The lesson here is that hard-to-treat cancers like glioblastoma require their own wardrobes, so to speak, not “hand-me-down” drugs made for other cancers.
A renewed focus on the daunting challenges presented by a cancer like glioblastoma can help thousands of people with cancer for whom the new “special sauce” treatments don’t work. It could also open new avenues for treating all types of cancer.
When a recalcitrant cancer like glioblastoma breaks all the prevailing rules, the remedy is to seek evermore unique models and tactics that focus on what makes it a distinctive outlier. Only by extricating ourselves from a one-size-fits-all mentality will truly novel treatments — not just ones that have worked elsewhere — emerge to afford individuals with recalcitrant cancer the same hope that a growing number of cancer patients have today.
David F. Arons, J.D., is the chief executive officer of the National Brain Tumor Society. He served on Vice President Joe Biden’s Cancer Moonshot Initiative’s panel of experts, is the current chair of the National Cancer Institute’s Council of Research Advocates, and serves on the institute’s Clinical Trial Advisory Committee.
This story has been updated to reflect recent reports that Sen. John McCain has glioblastoma.