Slipping Past Cancer's Barriers
Long gone are the days when cancer was believed to be a single disease, perhaps with varied manifestations in different body organs but otherwise fundamentally the same. Nowadays oncology textbooks report more than 200 cancer types, with a diverse spectrum of diseases even within individual organs. A seminal paper titled “The Hallmarks of Cancer,” published in 2000 by Douglas Hanahan and Robert Weinberg, reframed much of the discussion. In response, oncologists have shifted toward defining cancer by way of its properties—the characteristics that are common to all forms of the disease, and so form broad targets for treatment.
These hallmarks include their ability to invade adjacent tissue, and also set up colonies (or metastases) at distant sites in other organs; their callous indifference to the molecular screams of neighboring cells that are squeezed by their growth; their ability to evade the immune system and continue on their path of destruction; and their perennial Peter Pan complex—refusing to grow old and die, instead developing the ability to replicate indefinitely and avoid the normal preprogrammed cellular suicide (or apoptosis). Cancer can also command the body to build more blood vessels (called angiogenesis) to support its reckless growth.
In my group’s laboratories and elsewhere, researchers have found that cancer has another extremely nefarious ability: It can protect itself by hijacking the body’s biological barrier system, establishing protective bunkers that shield it from attack by drugs and the body’s own defenses. More generally, the way that cancer transports around substances with mass—molecules, cells, and even tissue—is quite different than what healthy cells do. In some ways all of cancer’s hallmarks are influenced, if not fully determined, by these mass transport differences, both at the molecular and the cellular level, as well as at locations near the tumor and elsewhere in the body.
Based on this observation, my colleagues and I have introduced the notion of transport oncophysics, and we now look at cancer as a proliferative disease of mass-transport dysregulation. We are using new technologies to understand how cancer hides and to break open these bunkers. One of the most promising approaches is targeting cancer with nanoparticles: multilayered, microscopic vessels that could attack a cancer even if it is hiding behind a series of barriers.