Harnessing Our Natural Defenses Against Cancer
One out of every two people will have to deal with a diagnosis of cancer during their lifetimes. The 10 percent of cancers that arise in genetically "high risk" groups alone represent less than 1 percent of the total population in the US, but cost a staggering $15 billion to treat annually.
Despite decades of research, the Holy Grail of a cure still eludes us, in part because of the fundamental, unstable nature of cancer—it easily produces variant cells that resist chemotherapies and this often results in relapse. Cancer is also difficult because different cancer types differ considerably in their biology, meaning that a single drug is unlikely to be effective against more than one or a few cancer types. Finally, even within a cancer type, different patients can have differences in how their cancers react to a given drug. What this all means is that "one drug that cures all," is not one drug, and unfortunately for metastatic cancer, often not a cure.
The problem is in many ways encapsulated by the following observation: for late-stage cancers, which are the most difficult to treat, most new drugs are considered a success if they extend life for several weeks or months. The limited or disappointing results of many chemotherapies has led to concerted efforts to identify the Achilles’ heel, or rather heels, of cancers.
If it’s any litmus test of where the most promising discoveries are being made, just read the titles any week of the world’s most prestigious scientific journals and parallel coverage in the popular press: it’s all about immunotherapies.
The idea makes sense: harness a patient’s own natural mechanisms for eliminating diseased cells, or give the patient man-made immune system components to help specifically target malignancies. This is certainly better, all else being equal, than injections of toxic drugs. Consider that the basic challenge of traditional chemotherapies is that they affect both cancerous and, to some extent healthy cells, meaning that for the drugs to work, doses must be carefully established to kill or arrest the growth of cancer cells, while keeping the patient alive. That is, the more drug, the more the cancer regresses, but the higher the chance of side effects or even patient death. This is problematic because many patents cannot withstand the doses of chemotherapies that are most likely to cure them, and even if they are, exposing rapidly dividing, mutation-prone cancer cells will strongly select for resistance to the therapy. Darwin got it right in his theory of natural selection, and his insights help us understand why remission is often followed by relapse.
Employing our own immune systems has intuitive appeal. Our bodies naturally use immunoediting and immune surveillance to cull diseased cells. However, the tumor microenvironment is a complex, adaptive structure that can also compromise natural and therapy-stimulated immune responses. This past year has seen important milestones. For example, based on promising clinical trials, the FDA recently approved a combination of two immunotherapies (Nivolumab and Ipilimumab) for metastatic melanoma. What one is not able to accomplish, the other is; this not only reduces tumor size, but is expected to result in less evolved resistance to either drug. This same idea of using combinations can be applied to immunotherapies together with many of the more traditional radiotherapies, chemotherapies, and more recent advances in targeted therapies.
Currently more than forty clinical trials are being conducted to examine effects of immunotherapies on breast cancer, with the hope that within a decade such therapies, if promising, can reduce or eliminate these cancers in the 1 in 8 women that currently are affected during their lifetimes. This would be truly amazing, headline news.
