From biomarkers to therapeutic targets—the promises and perils of long non-coding RNAs in cancer

Abstract

Biomarker-driven personalized cancer therapy is a field of growing interest, and several molecular tests have been developed to detect biomarkers that predict, e.g., response of cancers to particular therapies. Identification of these molecules and understanding their molecular mechanisms is important for cancer prognosis and the development of therapeutics for late stage diseases. In the past, significant efforts have been placed on the discovery of protein or DNA-based biomarkers while only recently the class of long non-coding RNA (lncRNA) has emerged as a new category of biomarker. The mammalian genome is pervasively transcribed yielding a vast amount of non-protein-coding RNAs including lncRNAs. Hence, these transcripts represent a rich source of information that has the potential to significantly contribute to precision medicine in the future. Importantly, many lncRNAs are differentially expressed in carcinomas and they are emerging as potent regulators of tumor progression and metastasis. Here, we will highlight prime examples of lncRNAs that serve as marker for cancer progression or therapy response and which might represent promising therapeutic targets. Furthermore, we will introduce lncRNA targeting tools and strategies, and we will discuss potential pitfalls in translating these into clinical trials.

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Acknowledgements

The authors wish to thank Katrien Van Roosbroeck for reviewing and editing the manuscript.

Funding

Research in the Gutschner lab is supported by funds from the intramural Wilhelm-Roux-Program of the Medical Faculty, Martin-Luther-University Halle-Wittenberg. Georg Richtig received funding from the Austrian Science Fund FWF (W1241) and the Medical University Graz through the Ph.D. Program Molecular Fundamentals of Inflammation (DK-MOLIN).

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Tony Gutschner conceptualized, wrote, and edited the manuscript. Georg Richtig wrote the manuscript and generated the tables. Monika Hämmerle prepared the figure and helped editing the manuscript and prepared tables. Martin Pichler contributed to manuscript editing.

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Correspondence to Tony Gutschner or Martin Pichler.

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Gutschner, T., Richtig, G., Haemmerle, M. et al. From biomarkers to therapeutic targets—the promises and perils of long non-coding RNAs in cancer. Cancer Metastasis Rev 37, 83–105 (2018). https://doi.org/10.1007/s10555-017-9718-5

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Keywords

  • lncRNA
  • PCA3
  • HOTAIR
  • MALAT1
  • ANRIL
  • GAS5
  • SPRY4-IT1