Cancer interception.

A common perception is that cancer risk reduction is passive, such as not smoking. However, advances in the understanding of cancer biology and in cancer treatment modalities suggest that it is now timely to consider anew cancer risk reduction by active, including pharmacologic, approaches. Risk avoidance approaches are certainly important, but other approaches are important as well, as exemplified by the irony that most new lung cancers occur in former smokers, or current avoiders. Cancer interception is the active way of combating cancer and carcinogenesis at earlier and earlier stages. A great challenge is to educate people that the development of cancers, like heart disease, typically takes years and accordingly can potentially be intercepted with risk-reducing agents in the same way that advanced cancers can be treated with drugs or that cardiovascular disease can be intercepted with antihypertensive and other risk-reducing drugs. The cancer biology behind cancer interception is increasingly solid. For example, hedgehog pathway studies of mutations in the patched homolog 1 (PTCH1) gene, which constitutively activates Smoothened (SMO), led to development of an oral SMO inhibitor active in advanced basal cell carcinoma and which, in very high-risk Gorlin syndrome patients (germ line PTCH1 mutation), is nearly completely clinically effective in intercepting basal cell neoplasia. Also, the oral immunomodulator lenalidomide, first found to be active in advanced, relapsed multiple myeloma, was highly effective in intercepting the precursor stage, high-risk smoldering multiple myeloma from progressing. These are but two exciting, recent examples of the many advances in cancer research that have created an optimal time to discover and implement cancer interception. The multifaceted roles of telomere maintenance in both fueling advanced cancers and, at early stages, keeping them at bay, also highlight how the growing knowledge of cancer biology opens avenues for cancer interception. Emerging molecular techniques, including next-generation sequencing platforms, that account for a large part of the remarkable recent advances in cancer biology are now being applied to interception of premalignancy. Keeping the medical community and public at large informed about possibilities for actively intercepting cancer will be important for gaining acceptance of this increasingly powerful approach to lessening the cancer burden.