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Targeting mTOR: A Little Bit of History and a Large Future

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mTOR Inhibition for Cancer Therapy: Past, Present and Future

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Abstract

The molecular target of rapamycin (mTOR) signaling pathway has been studied intensively for more than 20 years. These research efforts have been facilitated greatly by the serendipitous discovery and identification of rapamycin during a scientific expedition to Easter Island in 1964, highlighting the contribution of natural product discovery in unraveling important scientific and medical discoveries. Elegant work by several independent teams of investigators unraveled rapamycin’s unique mechanism of action through mTOR, sometimes called the master regulator of cell growth, energy utilization, metabolism, aging, and proliferation. Although several important conceptual gaps remain to be filled, the mTOR pathway is now understood at a level of molecular detail that rivals that of any other signaling cascade in mammalian cells. The exceedingly rapid rate of knowledge accumulation in this area stands as a tribute to the combined powers of chemical biology, yeast and Drosophila genetics, and biochemical and genetic studies in mammalian cells. The implications of targeting mTOR and related signaling elements to prevent and treat malignant and nonmalignant disorders with rapamycin and rapamycin analogs, called rapalogs, and possibly more versatile small molecule inhibitors, are astounding. Nonetheless, the challenges associated with the transition of rapamycin from the laboratory bench to the clinic have underscored the fact that we still have much to learn about the intricacies of the mTOR pathway itself, as well as the integration of this pathway into the network of signaling cascades that underpins the multitude of genetic subtypes that constitute cancer and other proliferative disorders. However, there is much optimism about making progress in this regard, given the immense headway made to date as introduced in this chapter and discussed more specifically throughout this book.

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  1. Department of Medicine, New York University, New York, NY, USA

    Eric K. Rowinsky MD

  2. Stemline Therapeutics, Inc, New York, NY, USA

    Eric K. Rowinsky MD

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Editors and Affiliations

  1. Samuel Oschin Comprehensive Cancer Inst Cedars Sinai Medical Center, Los Angeles, California, USA

    Monica Mita

  2. Samuel Oschin Comprehensive Cancer Inst Cedars-Sinai Medical Center, Los Angeles, California, USA

    Alain Mita

  3. Stemline Therapeutics, Inc., New York, New York, USA

    Eric K. Rowinsky

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Rowinsky, E.K. (2016). Targeting mTOR: A Little Bit of History and a Large Future. In: Mita, M., Mita, A., Rowinsky, E. (eds) mTOR Inhibition for Cancer Therapy: Past, Present and Future. Springer, Paris. https://doi.org/10.1007/978-2-8178-0492-7_1

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