Targeting Cancer Cells -- More Pathways, More Inhibitors, More Trials

Sara M. Mariani, MD, PhD
Introduction

Although some may be a bit puzzled by the ever-increasing number of small molecular inhibitors being tested for their anticancer activity, the limited efficacy shown by available compounds, the restricted range of activity, or the significant rate of resistance development is prompting researchers in academic and industrial laboratories to look for more and better inhibitors of cancer growth and survival.

Multiple signaling pathways or intracellular compartments are under the "microscope" for their potential therapeutic relevance in cancer treatment -- the insulin growth factor pathway (IGF), the mTOR pathway, the ubiquitin-proteasome system, histone deacetylases (HDACs), and Aurora kinases -- as illustrated by lead investigators at the 9th Annual Drug Discovery Technology World Congress, recently held in Boston, Massachusetts.

Targeted inhibitors are now available for most of these signaling pathways and systems. Multiple in vitro and in vivo testing is unveiling their characteristics and will ultimately determine which of them will indeed represent a viable strategy that meaningfully improves on current anticancer treatments.

As learned from the introduction of the first small molecular inhibitors in the past few years, activity, safety, tolerability (if long-term treatments are envisioned), and cost-benefit ratios will ultimately be the parameters determining their success for cancer patients. Identification of specific biomarkers and clinical end points to measure relative antitumor activity, as well as an accurate selection of responsive patients, will add to their applicability and clinical use.