Mutations Linked to Breast Cancer Treatment Resistance

It is known by laboratory oncologists that on-off switches and back up switches constitute the controls of cancer. When one of these switches stops working and a cell "short circuits," cancer is the result.

Study findings were reported a 2011 American Association of Cancer Research Meeting (AACR), on novel compounds that target two parallel circuits in cancer cells. These compounds, or small molecules, disrupt the signal that drives cancer cell survival and proliferation. While the profiles of each drug alone were of interest, the study found the profiles of the drugs in combination were better still.

The phenomenon of cross-talk defines an escape mechanism whereby cancer cells blocked from one passage, find a second. When therapists have the capacity to block more than one pathway, the cancer cell is trapped and often dies. This is what's observed with duel inhibitor combinations.

What was also interesting was the fact that these activities cut across various tumor types. Melanomas, colon cancers and lung cancers seem to have similar propensities to drive along these paths, demonstrating that cancer biology is non-linear. Cancers share pathways across tumor types in pathways that might not intuitively seem related.

It is the beauty of phenotype analysis that allows exploration of drugs and combinations that most clinicians wouldn't think of. It will be these counterintuitive explorations that will lead to meaningful advances.

You're right in that cancer medicine has learned a lot from HIV. A diagnosis of AIDS was a death sentence until the advent of drug cocktails in the 1990s, which helped patients suppress the disease indefinitely. Now researchers say a similar combination strategy may change the course of cancer. At least some researchers.

For a decade, researchers have crafted drugs to disrupt the precise cellular processes that fuel cancer. So far, survival benefits are measured in months, not years. That's because cancer, like HIV, evolves rapidly to evade a single treatment. Rather than mixing and matching approved drugs, scientists are now developing combinations designed to work in tandem to block cancer.

Among the most sought after attributes of chemotherapy drug combinations is drug synergy. Synergy, defined as supra-additivity wherein the whole is greater than the sum of the parts, reflects an elegant interaction between drugs predicated on their modes of action. While some synergistic interactions can be predicted based upon the pharmacology of the agents, others are more obscure.

The application of synergy analyses may represent one of the most important applications of the functional profiling platform (phenotype analysis); enabling clinicians to explore both anticipated and unanticipated favorable interactions.

Equally important may be the platform's capacity to study drug antagonism wherein two effective drugs counteract each others’ benefits. This phenomenon, characterized by the whole being less than the sum of the parts, represents a major pitfall for clinical trialists who simply combine drugs because they can.

The problem with these "targeted" drugs is the same thing that was a problem with AZT for HIV/AIDS. Early results, then rapid resistance. The solution is "combination therapy" to attack all the different targets. It's going to take "combination" anti-vascular therapy to make the big difference, but this is definitely coming and it's the most promising thing on the therapeutic horizon.