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Dysfunction of the RB Retinoblastoma Gene in Cancer

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Checkpoint Controls and Targets in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The retinoblastoma gene RB, which was the first tumor suppressor gene to be identified, is a key regulator of the cell cycle and its inactivation, either direct or indirect, underlies multiple types of human tumors. Consistent with its role as tumor suppressor, it is well established that RB inhibits cell proliferation by binding to the E2F family of transcription factors thereby repressing genes that are required for the G1–S transition of the cell cycle. However, in the past decade, a myriad of studies focusing on the role of RB in cancer development implicated RB in many cellular processes that could all contribute to its tumor suppressor function, suggesting that the role of RB in cancer is much more complex than previously thought. To further complicate matters, the other members of the RB family, retinoblastoma-like 1 (RBL1 or p107) and retinoblastoma-like 2 (RBL2 or p130), have both overlapping and distinct functions compared with RB and many cellular functions of RB are mediated by over a hundred interacting proteins and numerous transcriptional targets. Now, emerging evidence shows that RB status can influence the response to different anti-cancer therapeutics according to the context. Therefore, a thorough understanding of all RB functions in cancer is more crucial than ever.

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Acknowledgments:

The authors would like to thank the members of Giordano’s lab for their helpful comments. The authors apologize for having cited reviews in some instances, rather than many excellent primary papers, owing to the broadness of the topic and the space constraints.

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Authors and Affiliations

  1. CROM – Center of Oncology Research Mercogliano, Avellino, Italy

    Francesca Pentimalli, Letizia Cito & Antonio Giordano

  2. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA

    Francesca Pentimalli & Antonio Giordano

  3. Department of Human Pathology and Oncology, University of Siena, Siena, Italy

    Antonio Giordano

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  1. Francesca Pentimalli
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  2. Letizia Cito
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Correspondence to Antonio Giordano .

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  1. M.D. Anderson Cancer Center, University of Texas, Holcombe Blvd. 1515, Houston, 77030, U.S.A.

    Zahid H. Siddik

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Pentimalli, F., Cito, L., Giordano, A. (2010). Dysfunction of the RB Retinoblastoma Gene in Cancer. In: Siddik, Z. (eds) Checkpoint Controls and Targets in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60761-178-3_8

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