Glioblastoma, a formidable foe, faces a ‘reservoir of resilience’ in McCain

Sen. John McCain (R-Ariz.) returned to the Capitol July 25 to cast what was a tie-breaking vote to proceed to debate a bill to repeal Obamacare. AP Photo/Andrew Harnik

As a naval aviator, John McCain was shot down during the Vietnam War and spent five and a half years as a prisoner of war. He received inadequate medical care for injuries that nearly killed him, enduring years of unimaginable deprivation and torture.

He persevered with a remarkable resilience and fighting attitude that made him an American hero and helped him grow into the role of public servant and, as a United States senator, a leader on a national stage.

Now, McCain faces another remorseless enemy that will again test him in body and spirit – glioblastoma, a malignant brain cancer that kills about 13,000 Americans each year.

As the co-director of the Preston A. Wells Jr. Center for Brain Tumor Therapy at the University of Florida, I engage continually with patients and their families in the battle against glioblastoma. And I know firsthand how patients can often be swept into despair by the devastating diagnosis.

The news of McCain’s condition – and his return to Washington July 25 to participate in the health care vote – provides an opportunity to remind the public about important and potentially game-changing research into therapies with the promise of greatly extending survivability for those with glioblastoma. Some of these therapies are in clinical trials and offer the ultimate hope of someday turning a cancer perceived as a quick killer into a curable disease.

Stats are one thing, but people are another

One thing often misunderstood by the public when talking about cancer in general is survivability. Projections for how long a person might be expected to survive are just that – projections. Each person is different, and each person’s cancer is different.

In the case of glioblastoma, survivability is 15 to 18 months, with standard treatments such as surgery, chemotherapy, radiation and, recently, alternating electric field therapy. These very short survival times cast an understandable pall over talk of the disease.

We also know, however, that some patients with the cancer, with even just standard treatments, have lived very long – even decades after their diagnosis. Granted, those numbers are a small subset of patients. But we do measure two- to three-year survival rates, and now from some promising clinical trials, five- and 10-year survival rates.

Glioblastomas typically arise from genetic changes to cells inside the brain. There is no behavior that contributes to their random appearance, and there are no clear risk factors.

And, there is no definitively curative therapy for glioblastoma. It is a relentlessly aggressive tumor. What makes these cancer cells so challenging is the fact that they migrate in the brain, very far from the origin of the tumor. Though surgeons can remove a large percentage of the tumor cells, unfortunately, islands of invasive cells remain. They often move into other areas of the brain that we cannot eradicate with surgery. Radiation and chemotherapy can slow the growth of invasive brain tumor cells, but limitations on the intensity of these treatments that can be tolerated within the brain and the existence of resistant tumor cells hinder the overall effectiveness.

Enlisting the immune system

While patients with glioblastoma, like all patients with cancer, often feel as if they have been betrayed by their own bodies, it is one of the most remarkable aspects of every person’s physical makeup that provides perhaps the greatest promise in fighting the disease: the immune system.

Using the immune system to fight cancer is not a new concept. The idea that the immune system could be goaded into potentially recognizing cancers and lead to their rejection was advanced more than a century ago. But the science and our understanding of the immune system and human genomics required time to catch up to our ambitions.

Immunotherapy, combined with an ever-increasing understanding of genomics, leaves us on a cusp of a revolution in cancer treatment.

A pipette and test tubes in a lab such as those used to research immunotherapy. CI Photos/Shutterstock.com

In genomics, we seek to understand how genes are altered in cancer. We can profile a patient’s tumor and understand the landscape of alterations that are present in those cancer cells. That has allowed us in some cases to predict how those tumors are likely to behave. It also allows us in some cases to select therapies that may be more effective in targeting those cancers.

We can also identify specific proteins produced by these tumor cells and essentially program immune cells to home in on them and kill the cancer. This leads to a personalized treatment approach where you direct a patient’s immune system against a cancer, boosting or enhancing a patient’s immune response against specific alterations found in their tumor.

At the University of Florida, one of the immunotherapy approaches we are advancing is called adoptive T cell therapy. In this work, we generate large numbers of “killer T cells” designed to recognize a patient’s specific tumor and transfer those T cells back to the patient with the hope that these activated cells can seek out and destroy remaining tumor cells. We have active clinical trials exploring this approach in patients with aggressive brain tumors.

Additionally, we are exploring new ways to take advantage of drugs called immune checkpoint inhibitors, which elevate the activation state of the immune system of a patient so that it can more effectively combat cancer.

We currently do not have any immunotherapies that are approved by the Food and Drug Administration for the treatment of brain cancer, although a number are being investigated in clinical trials at UF and other leading medical centers.

One of the things we know about our immune system is that it is essentially designed to handle almost an infinite number of unknown external threats. It’s a remarkable system that, once harnessed, might be the most effective tool in battling brain cancers.

A matter of heart

But perhaps one of the most critical tools fighting glioblastoma is the one that is in McCain’s own heart. It is the will to fight and engage an enemy. It is the resilient spirit to battle against great odds.

John McCain on the presidential campaign trail in 2008 in Fayetteville, North Carolina. Reuters/Brian Snyder

We all have experienced in the field of clinical research or clinical care those patients whose outlook and approach to tackling their disease seems to lead to better outcomes. We don’t necessarily have a quantitative assessment of how these factors impact the duration and quality of life in patients battling cancer, but we seem to agree that they matter.

With glioblastoma, we can’t ignore what the data and the numbers tell us about its aggressiveness. But I think bringing to bear all your personal resources, spiritual and emotional support and the obstinate will to fight can lead to better outcomes.

And nobody doubts John McCain’s deep reservoir of resilience.