Category: Oncology

Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.

Shay Soker, PhD, is Professor, Regenerative Medicine, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine.
Aleksander Skardal, PhD, is Assistant Professor, Regenerative Medicine and Biomedical Engineering, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine.

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This volume provides an integrated account of our current understanding of the functions of D-type cyclins during development and tumorigenesis, with special emphasis on the kinase-independent functions of these proteins. The volume will provide a thorough review of the latest discoveries on the new functions and interacting partners of mammalian cyclin Ds crucial to explain their oncogenic and differentiation properties in different cellular contexts. The volume begins with a historical perspective of how D-type cyclins were first discovered and eventually cloned from cancer tissues, followed by an account on the canonical functions of cyclin Ds during the G1-S transition of the cell cycle. Several chapters will be devoted to review the functions of D-type cyclins as transcriptional regulators and the mechanisms through which these novel functions could impact the tumorigenic process. Also discussed is emerging evidence that points to a role of D-type cyclins, particularly cyclin D1, as a cytoplasmic regulator of various cellular functions. This property, in human cells at least, is traceable to certain splice isoforms with novel oncogenic implications. Finally, a chapter is devoted to recent efforts to revise the canonical view of the “retinoblastoma pathway” to incorporate new evidence that suggests that cyclin D1’s role in G1 is to singly-phosphorylate the retinoblastoma protein (pRb) for discrimination of target protein interactions. This work represents a significant departure from the view of cyclin D1 as a negative regulator of pRb and may have critical implications for understanding the function of antineoplastic agents that target the cyclin D1-associated kinases.

This volume provides an integrated account of our current understanding of the functions of D-type cyclins during development and tumorigenesis, with special emphasis on the kinase-independent functions of these proteins. The volume will provide a thorough review of the latest discoveries on the new functions and interacting partners of mammalian cyclin Ds crucial to explain their oncogenic and differentiation properties in different cellular contexts. The volume begins with a historical perspective of how D-type cyclins were first discovered and eventually cloned from cancer tissues, followed by an account on the canonical functions of cyclin Ds during the G1-S transition of the cell cycle. Several chapters will be devoted to review the functions of D-type cyclins as transcriptional regulators and the mechanisms through which these novel functions could impact the tumorigenic process. Also discussed is emerging evidence that points to a role of D-type cyclins, particularly cyclin D1, as a cytoplasmic regulator of various cellular functions. This property, in human cells at least, is traceable to certain splice isoforms with novel oncogenic implications. Finally, a chapter is devoted to recent efforts to revise the canonical view of the “retinoblastoma pathway” to incorporate new evidence that suggests that cyclin D1’s role in G1 is to singly-phosphorylate the retinoblastoma protein (pRb) for discrimination of target protein interactions. This work represents a significant departure from the view of cyclin D1 as a negative regulator of pRb and may have critical implications for understanding the function of antineoplastic agents that target the cyclin D1-associated kinases.