I may have written my book Why Millions Survive Cancer: The Successes of Science a little too early. In this book I compiled evidence that progress was being made in the field of cancer. The book discusses the sharp decline in deaths from lung cancer thanks to our understanding of the carcinogenic effects of cigarettes and kicking the habit. It discusses the success of screening methods that allow doctors to catch the disease early for a better prognosis, and for removing precancerous lesions for prevention. The first cervical cancer vaccine and procedures that allowed women undergoing chemotherapy to keep their fertility were celebrated, along with new molecularly targeted therapies. The book was published in 2011.
The time for optimism in the field of cancer research is now -- a time that Science magazine named "cancer immunology" as the breakthrough of the year. Today we have the hope that the cure for cancer is inside ourselves -- in our immune system.
Yes, we have made great strides in understanding many major pathways of abnormal growth, a hallmark of cancer. Strategies to develop new drugs based on this molecular understanding gave us a new armory of treatments such as Gleevec for leukemia and Herceptin for breast cancer, among many other new molecularly targeted drugs designed to stop tumor growth.
But abnormal growth is just one part of the definition of cancer, a set of diseases characterized by abnormal growth and the ability to spread or metastasize. It is the ability of cancer cells to metastasize that is the obstacle to a cure. Surgery can cut out a tumor, and drugs can halt growth and cause cell suicide, but how can we eliminate all metastasizing cells?
Most biologists will admit that a comprehensive understanding of the cell and molecular complexities of the disease is far from reach. We have identified many molecular characteristics of tumors and appreciate the variability between patients and over time, but how will we ever be able to act on all of the genetic and epigenetic information? Perhaps we will never have to.
The immune system has an infinite capacity for recognizing and eliminating invaders, including tumor cells. But the immune system is often suppressed by a tumor. Great progress has been made by being able to overcome the suppression of the immune system. What better way of mopping up metastasizing cells?
Melanoma was a cancer that had few treatment options and none that could extend life. This changed in 2011, when the Food and Drug Administration approved a drug called ipilimumab, developed by Bristol-Myers Squibb. The drug consisted of an antibody that would overcome the suppression of the immune system by blocking an inhibitor molecule of T cells called cytotoxic T-lymphocyte antigen 4 (CTLA-4). Results were dramatic and durable for some: Out of 1,800 patients treated with ipilimumab, 22 percent were alive three years later. Like with most drugs, not all patients respond, and for some, severe side effects appeared from an overactivated immune system. But it is early days.
This immunotherapy approach has potential for many types of cancer, but the real excitement is over the possibilities of durable responses -- results that last for years or even decades. And why not? We know that vaccinations provide protection over decades.
Another approach that utilizes a patient's immune system is also being explored. This is more complicated and involves personalized treatment in which a patient's T cells are removed and genetically modified to make them target a tumor cell. It uses synthetic biology to synthesize chimeric antigen receptors known as CARs to create "serial killer" T cells. The approach is in several clinical trials, and pharmaceutical companies such as Novartis are gearing up to facilitate personalized T-cell therapy.
New studies regarding the mechanisms of metastasis are likely to yield treatments that complement immunotherapy approaches. For example, David Lyden, and colleagues reported that exosomes, small membrane-bound bubbles of information released by tumor cells, are important means for communication for metastasizing cells. Could this be a new target to prevent metastasis?
One point is certain. We are finally reaching the heart of the cancer problem: How can we stop and eliminate metastasizing cancer cells? With these new developments on the horizon, I may just have to pick up my pen again.