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Perspective

Cancer Research Frontiers. 2015 Sep; 1(3): 237-252. doi: 10.17980/2015.237

Components of the Linker of the Nucleo- and Cytoskeletal Complex (LINC) as Novel Molecular Targets for Small Cell Lung Cancer.

Susan D. Mertinsa*

aMolecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Diagnosis and Treatment, National Cancer Institute at Frederick, Frederick, MD 21702

 

*Corresponding author: Susan D. Mertins, Molecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Diagnosis and Treatment, National Cancer Institute at Frederick. P.O. Box B, Bldg. 315, Room 6, Frederick, MD 21702. Phone: 1-301-846-7245; Email: smertins@mail.nih.gov

Citation: Susan Mertins. Components of the Linker of the Nucleo- and Cytoskeletal Complex (LINC) as Novel Molecular Targets for Small Cell Lung Cancer. Cancer Research Frontiers. 2015 Sep; 1(3): 237-252. doi: 10.17980/2015.237

Copyright: @ 2015 Susan Mertins. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing Interests: The author declares that she has no competing interests. The views in this paper are those of the author and do not necessarily reflect the position of the US Government.

Received March 31, 2015; Revised June 29, 2015; Accepted July 1, 2015.

 

ABSTRACT

Small cell lung cancer (SCLC) is a recalcitrant cancer and likely due to environmental insults as nearly 90% of the patients have tobacco exposure. Chemotherapy is the standard of care but it rarely affects complete cures and drug resistance is common. While a vast number of clinical trials with both cytotoxic and molecularly targeted therapies have been conducted, no new agents for SCLC patients have reached oncology practices since the 1980s. Thus, there is a pressing need to identify novel molecular targets and effective therapies. In this Perspective, an overview of the putative source cell for SCLC, the neuroepithelial cell, will be presented to aid in the selection of novel drug targets. In particular, neuroepithelial cells are chemosensory and mechanosensory in function, regulating responses to oxygen tension, carbon dioxide, pH, and stretch. A panopoly of secretory factors, both peptidinergic and adrenergic, are released and in numerous experimental systems, shown to communicate with efferent neurons. Because it would be expected that the components of signal transduction pathways active in such functions are intimately connected to cell survival, these proteins are potential drug candidates. One example would be the complex set of proteins residing in the nuclear envelope, the LINCs, (or linkers of the nucleo- and cytoskeletal complex) which provide physical and biochemical signals to and from the extracellular environment and the nucleus. Furthermore, cell-based high content screens are amenable to discovery efforts targeting LINCs.

Keywords: small cell lung cancer, linkers of the nucleo- and cytoskeleton complex, neuroepithelial bodies, nesprins, COSMIC database, molecular targets

 

 

 

 

 

 

 

 

 

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