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CRISPR-Cas deployment in non-small cell lung cancer for target screening, validations, and discoveries

Cancer Gene Therapy volume 28, pages 566–580 (2021)Cite this article

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Abstract

Continued advancements in CRISPR-Cas systems have accelerated genome research. Use of CRISPR-Cas in cancer research has been of great interest that is resulting in development of orthogonal methods for drug target validations and discovery of new therapeutic targets through genome-wide screens of cancer cells. CRISPR-based screens have also revealed several new cancer drivers through alterations in tumor suppressor genes (TSGs) and oncogenes inducing resistance to targeted therapies via activation of alternate signaling pathways. Given such dynamic status of cancer, we review the application of CRISPR-Cas in non-small cell lung cancer (NSCLC) for development of mutant models, drug screening, target validation, novel target discoveries, and other emerging potential applications. In addition, CRISPR-based approach for development of novel anticancer combination therapies is also discussed in this review.

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Fig. 1: CRISPR-Cas editing can be used during the initial phase of development wherein cell lines with desired mutations can be rapidly designed and checked for drugs under development or cell lines can be screened using varieties of guide RNA (sgRNA) to discover new targets.
Fig. 2: Influence of KEAP1/Nrf2 pathways on acquired resistance mechanisms.
Fig. 3: Multiple emerging applications of CRISPR-Cas systems for use in NSCLC.

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Acknowledgements

We thank Jatin Vimal for his insightful suggestions. We are grateful to Levim Biotech LLP for its support in fostering industry-academia collaborations and furthering fundamental research in the field of genetic engineering.

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  1. School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamilnadu, India

    K. Sreedurgalakshmi & Reena Rajkumari

  2. Division of Biosimilars and Gene Therapy, R&D, Levim Biotech LLP, Chennai, Tamilnadu, India

    K. Sreedurgalakshmi & R. Srikar

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Sreedurgalakshmi, K., Srikar, R. & Rajkumari, R. CRISPR-Cas deployment in non-small cell lung cancer for target screening, validations, and discoveries. Cancer Gene Ther 28, 566–580 (2021). https://doi.org/10.1038/s41417-020-00256-7

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