Photo credit: Kirsten Luce for The New York TImes
Once thought to be a single disease which could potentially be cured with a single magic bullet, cancer has long resisted our often simplistic efforts to overcome it. The complexity of cancer―simultaneously both a part of us as well as a hostile invader―demands smarter strategies. Fortunately, recent breakthroughs have highlighted a promising path forward for improving patient outcomes.
The brilliance of these breakthroughs comes from an appreciation of the individuality of each patient. As Siddhartha Mukherjee, M.D., put it in his recent New York Times editorial, “Every cancer is characterized by its distinctive marks: a set of individual scars stamped on an individual genome. The iconic illness of the 20th century seems to reflect our culture’s obsession with individuality.”
In his piece, Mukherjee―the oncologist behind the Pulitzer Prize-winning biography of cancer, The Emperor of All Maladies and whose new book The Gene: An Intimate History comes out this week―explores just how radically our attitude toward curing cancer has changed in the past decade. Previously, “cancers were lumped into categories based on their anatomical site of origin,” and “the prospect of personalizing therapy was frowned upon.” Once “trained to follow rules, oncologists are now being asked to reinvent them…to assess the particular personality and temperament of an individual illness, so that [they] can tailor a response with extreme precision.”
Specifically, Mukherjee focuses on two approaches to conquer cancer’s complexity. The first recognizes that while no two tumors have the exact same genetic mutations, the behaviors affected by those mutations―such as growth, migration, and blood vessel formation―often overlap. For instance, let’s say individual mutations in gene A, gene B, and gene C all lead to increased cancer cell growth, through the activation of pathway X. To target the mutations directly, separate drugs would be needed to treat patients with the different mutations.
Alternatively, a drug that targeted pathway X could treat patients regardless of whether their cancer had a mutation in gene A, gene B, or gene C. By identifying the behaviors exploited by the cancer and then disrupting the pathways that fuel those behaviors, a single medicine could potentially be used to treat a wider range of patients.
Unfortunately, tumors also have an uncanny ability to evolve and outsmart our efforts to stop them. If cancer cells rely on an overactive pathway X to grow, and are then treated with a drug that blocks pathway X, it’s possible that the cancer cells could mutate further and shift their capacity for growth to a different pathway, thus rendering the pathway X drug useless. Therefore, while this represents an improvement over previous practices, its methodology remains quite simplistic. If we want to truly vanquish cancer, this could serve as a useful tool, but should ultimately be complemented by other tactics that can match cancer’s diversity and flexibility.
This brings us to the second approach, one that provides a “solution to the impasse of unlimited diversity” and enables patients to confront cancer in all its complexity, with a tool that they’ve possessed all along: their own immune systems.
This strategy, which the Cancer Research Institute has pioneered since 1953, is called immunotherapy, and while several forms of immunotherapy exist, all promote the same goal: to harness the power of the immune system by activating an immune response against the “foreign” cancer cells. By virtue of the immune system’s adaptability, specificity, and memory, immunotherapy has already led to amazing successes in patients with advanced skin, lung, kidney, and blood cancers.
"We're very excited to see the field we pioneered catching on and getting the resources needed to help more and more patients… Immunotherapy's made everyone stand up and take notice, but it's still at the start."
Whereas anti-cancer drugs can only target specific markers on cancer cells and become useless if the cells ditch that marker, the cells of the immune system―enhanced by immunotherapy―can keep pace with the cancer cells in the mutational arms race. Sometimes, in cases where the cancer cells are already heavily mutated and appear very “foreign,” all the immune system needs is a little boost. This boost is provided by a type of immunotherapy called checkpoint inhibitors, which enables anti-cancer immune cells to ignore cancer’s attempts to suppress them. In other cases where the cancer cells have fewer mutations and are better at hiding their identity, doctors can tell the immune system what to look for.
This can be done in several ways: vaccines that provide intelligence to the immune system, customized viruses that infect cancer cells and draw the immune system’s attention to them, and even genetically modifying a patient’s immune cells to enhance their ability to target and destroy tumors.
Furthermore, chemotherapy drugs are effective only while they remain in the body, while anti-cancer immune responses have the potential to persist long after the initial immunotherapy drugs have left the body. As a result, immunotherapy can offer patients long-lasting protection. Already, immunotherapy has significantly improved long-term outcomes in melanoma patients. Historically, the five-year survival rate for patients with advanced melanoma is 17%, while twice the amount of patients―34%―have survived to at least the five-year mark after being treated with a checkpoint inhibitor immunotherapy.
The results thus far are impressive and should give everyone great hope for the future; however, much work remains to be done to further improve and extend immunotherapy’s benefits. As our CEO and director of scientific affairs, Jill O’Donnell-Tormey, Ph.D., said, "We're very excited to see the field we pioneered catching on and getting the resources needed to help more and more patients… Immunotherapy's made everyone stand up and take notice, but it's still at the start."