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

Belinda Seto

doi:10.1186/2001-1326-1-29

Abstract

Rapamycin was discovered more than thirty years ago from a soil sample from the island of Rapa Nui. It was isolated from Streptomyces hygroscopicus and initial characterization focused on its antifungal activities. Subsequent characterization showed that it has immunosuppressive properties and has been used successfully to reduce organ rejection with kidney transplantation. Rapamycin has proven to be a versatile compound with several seemingly unrelated properties, including antifungal, immunosuppressive, and anticancer. The National Cancer Institute (NCI) Developmental Therapeutics Program demonstrated that rapamycin inhibited cell growth in tumor cell lines. These observations stimulated research to explore the underlying mechanism of anti-tumor activities. Cell growth inhibition involves binding to the mammalian Target of Rapamycin (mTOR). The mTOR signaling pathway is critical to cell growth, proliferation, and survival and rapamycin inhibits these hallmark processes of cancer. Binding of growth factors activates mTOR signaling, which in turn leads to downstream phosphorylation of protein kinases, e.g., p70S6 kinase and lipid kinases in the phosphorylation of phosphoinositides. Understanding of mTOR signaling provided the biological basis for targeted chemotherapeutics development, including several rapamycin analogues for treating breast and other cancers.

Highlights

Breast cancer is the second most commonly diagnosed cancer, after skin cancer, among U.S women
Recent developments in computed tomography imaging have improved the early detection of breast cancer, when treatment is most effective [2]
This confluence of technology development in early diagnosis and improved therapeutics has led to a decline in breast cancer death in recent years, death rates are still higher than all types of cancer other than lung cancer [3]

Summary

Introduction

Breast cancer is the second most commonly diagnosed cancer, after skin cancer, among U.S women. This is another example that illustrates the partnership between the federal government and the industrial partners that is the cornerstone of clinical translational research Another NIH program that facilitates small molecule screening is the Molecular Library Screening Centers Network (MLSCN), established in 2008, to provide large-scale screening capacity necessary to identify small molecules that can be optimized as chemical probes to study the functions of genes, cells, and biochemical pathways in health and disease. These small molecules may be used by researchers in the public and private sectors to validate new drug targets, which could move into the drug-development pipeline. The enhancement of the armamentarium for breast cancer should continue to reduce the mortality and morbidity for patients

Conclusion

Findings

24. Abraham RT