Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer

Breast cancer is the second most commonly diagnosed cancer, after skin cancer, among U.S. women. In 2012, 227,000 new cases have been reported [1]. Recent developments in computed tomography imaging have improved the early detection of breast cancer, when treatment is most effective [2]. Concomitant with the technological development is the explosion of research findings on the molecular mechanisms of breast cancer. As a result, mechanism-based approaches have become increasingly used as strategies for therapeutic developments. This confluence of technology development in early diagnosis and improved therapeutics has led to a decline in breast cancer death in recent years, although death rates are still higher than all types of cancer other than lung cancer [3].This report describes a tale of discovery that reinforces the serendipitous nature of basic research and the notion that discoveries may lead to unanticipated outcomes in other disciplines. In this particular story, the isolation of the bacterium Streptomyces hygroscopicus from a soil sample three decades ago on a remote island led to intense, multifaceted research that changed the way breast cancer is treated. The identification of rapamycin from Streptomyces hygroscopicus as an antifungal agent, through being an immune inhibitor to being an effective anticancer drug, demonstrates a research continuum driven by clinical observations that were critical in the elucidation of the mTOR pathway. Rapamycin provided the stimulus for research on the complex and pivotal mTOR pathway that transmits signals through which it controls a range of vital biological processes. The dissection of the molecular networks of interacting signaling pathways has led to improved understanding of the transcription, protein synthesis, and metabolic processes that underpin oncogenic transformation. Such knowledge has led to therapeutic developments that yielded targeted drugs for breast cancer patients. For patients who are estrogen and