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Therapeutic Anticancer Approaches Targeting Telomerase and Telomeres

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Multi-Targeted Approach to Treatment of Cancer

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Abstract

Telomeres and telomerase are attractive targets for anticancer therapy. This is evidenced with the facts that majority of human cancers express the enzyme telomerase which is utmost important to maintain the telomere length, thereby to ensure indefinite cell proliferation – a hallmark of cancer. In human cells, a structure referred to as telomere has been identified to cap the terminal regions of chromosomes which can protect the ends of DNA strands from degradation and fusion, whereas telomerase plays a pivotal role in cellular immortality and tumorigenesis. Henceforth, strategies have been made to induce telomerase inhibition target virtually all of the major components of ribonucleoprotein holoenzyme and related cell signal pathways that regulates its activity which includes telomerase reverse transcriptase (hTERT) catalytic subunit, the telomere RNA component (hTERC), and associated proteins. It is noteworthy here that most of the cancers have an alternative lengthening of telomere termed as ALT even in the absence of telomerase activity. In these cases, there is an urgent need to understand the cell signaling pathways for ALT mechanism which can be used as therapeutic targets. Other strategies have been developed to target the protein associated with telomerase at the telomeric ends of chromosomes such as tankyrase. Increasing evidences suggest that directly targeting telomeric DNA using agents directed against the shelterin complex may also have anticancer activity. The limitations of strategies remain to be resolved to facilitate the clinical applications. In this chapter, recent development of strategies against these targets shall be discussed.

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Authors and Affiliations

  1. Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Deeksha Pal, Ujjawal Sharma & Rajendra Prasad

Authors
  1. Deeksha Pal
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  2. Ujjawal Sharma
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  3. Rajendra Prasad
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Corresponding author

Correspondence to Rajendra Prasad .

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Editors and Affiliations

  1. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Varsha Gandhi

  2. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Kapil Mehta

  3. Delhi State Cancer Institute (East), Delhi, India

    Rajesh Grover

  4. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Sen Pathak

  5. Department of Bioimmunotherapy, Section of Cytokine Research, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Bharat B. Aggarwal

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Pal, D., Sharma, U., Prasad, R. (2015). Therapeutic Anticancer Approaches Targeting Telomerase and Telomeres. In: Gandhi, V., Mehta, K., Grover, R., Pathak, S., Aggarwal, B. (eds) Multi-Targeted Approach to Treatment of Cancer. Adis, Cham. https://doi.org/10.1007/978-3-319-12253-3_18

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