When my father was misdiagnosed with tuberculosis in 1973 we soon learned that the real disease was cancer. It was in his lungs, but had started elsewhere. His first operation removed part of a lung, and he came home, but was soon back in Temple University Hospital with a second operation, and in his weakened state he never left the hospital again. I visited every day after school, learning to massage his atrophying back muscles and imagining his body invisible warrior cells fighting back against the cancer along with the chemicals and radioisotopes. But he knew, before I did, that there was no cause for optimism. His army of immune defenses and therapies all failed him.
I was still in high school but had spent summers working at a Temple University lab, learning about gene mapping alongside cancer researchers. I had seen that progress was very slow, and for my father it was decades too slow to save him.
Techniques for fighting cancer have evolved since then. Harsh chemical and radiation treatments have become more precise, though they are still very toxic. Immunotherapy has emerged which highlights cancer and identifies it for the immune system to attack. Unfortunately cancers mutate so often these treatments have limited effectiveness. Sometimes these new therapies lead to miracle cures as with my childhood friend Ira who is still in remission a decade after receiving a new immunotherapy for pancreatic cancer, but for most, these remissions for solid tumors are short lived.
When my father died in 1973, cancer represented 17.7% of all deaths. Today that number has grown to 25.5%. And cancer is often a protracted and painful death which makes it particularly impactful as you are likely to know, and as I do. Perhaps some of the statistical increase is due to longer life expectancy, or perhaps due to improved diagnostics that put more deaths into the cancer column. But adjustments aside, it is clear that despite improved diagnostics, preventative knowledge and treatment advances that at least allow us to win a few battles, we are still losing the war against many cancers.
The biggest advance of recent years has been the introduction of immunotherapy treatments. Keytruda, Revlimid and CAR-T, to name just a few, have been heavily publicized. There are over 3,000 trials of prospective immunotherapies currently underway. Almost all are focused on cell membrane proteins involved in overcoming the cancer's ability to hide from the immune system. These immunotherapies are a great advance, and while the vast number of trials is exciting, there is not a single one of them using this paradigm that is likely to generate anything close to the kind of moonshot breakthrough that we all wish for.
A fundamentally different approach has been developed at Baylor College of Medicine by Dr. Bert O’Malley. He focuses on a specific type of immune cell, a T cell known as T reg, which is the quarterback of the immune response to cancer. Whereas at first it alerts the immune system to the presence of the cancer and brings inflammation to bear, it soon turns off and regulates the immune response away as the cancer grows. But when a single gene is deleted (Steroid Receptor Coactivator -3) the T reg cell then reactivates the inflammation (cytokines, interleukins, other T cells) and the cancer is doomed. Initial studies in animals have been almost 100 percent successful in breast, prostate, brain and pancreatic cancers.
O’Malley’s approach is noteworthy because it works in the cell nucleus, rather than the cell membrane where other immunotherapies work. Perhaps for that reason, the treatment also shows little toxicity. The altered cells proliferate and take over, which means a single treatment may be enough to last for the patient’s life, as has been shown in the animal studies. Human trials are next.
Since President Nixon first announced his war on cancer in 1971, knowledge of genes and of cancer has exploded. The technology that allows researchers like those at Baylor to accurately pinpoint and change genetic material was like science fiction then. Neither Nixon nor my father could have imagined the genetic editors that O’Malley and his group use to turn the immune quarterback around and back into the fight.
Every once in a while I still hear a voice that reminds me of my father. The association is always a painful shock, and yet I root for the day when that remembered voice is embodied in someone who is surviving the very same deadly killer that took my dear dad.
