The finding that hsp90, a "molecular chaperone" that shuttles proteins throughout cells and performs a critical role in the mitochondria of tumor cells could have a profound influence on the development of an emerging class of drugs. It may help explain the limited effectiveness of current hsp90 inhibitors, which do not get into the mitochondria. The authors of the paper describing the work show that an hsp90 inhibitor that does get into the mitochondria has profound cell-killing capabilities.

In May of this year, two major scientific journals published papers correlating response to Iressa, AstraZeneca's targeted therapy for refractory non-small cell lung cancer, to a series of mutations clustered in a section of the EGFR gene. These widely publicized findings are fueling discussions that are bound to have consequences not only for AstraZeneca, patients and clinicians, but also for many pharmaceutical companies working on targeted therapies.

Despite the success of Gleevec, developing drugs that inhibit complex signaling pathways, while simultaneously trying to understand the biology around a drug's target, remains a challenge. Without biomarkers to help establish dosing and identify likely responding patients, clinical development of targeted cancer drugs will remain challenging. AstraZeneca's recent experience with Iressa bears this out. It's likely that single markers will not be sufficient to stratify patients by their tumor types; rather, patterns of gene and protein expression will be required. The technology to take these measurements is making its way from academia to industry, but the process is slow, and needs encouragement and better coordination between academia, regulators, and industry. Meanwhile, clinical trials themselves remain the best target validation tools. When all is said and done, efficacy is the best biomarker.