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KRAS as Potential Target in Colorectal Cancer Therapy

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Natural Bio-active Compounds

Abstract

Colorectal cancer (CRC) is among the most commonly diagnosed cancers affecting both genders in the world. It is characterized by genetic instability, which drives tumor formation via the activation of oncogenes, such as KRAS and B-RAF. Approximately 40% of CRC patients harbor the mutated KRAS oncogene as the predominant form of RAS mutation which plays a key role in the early development of cancer adenoma. The constitutively mutated K-Ras protein is able to bypass signals from its upstream effector, epidermal growth factor receptor (EGFR), thus rendering the existing anti-EGFR treatments (cetuximab and panitumumab) ineffective. However, there is no direct anti-KRAS treatment showing clinical benefits despite several decades of comprehensive efforts. To date, many efforts have been done to target the aberrant KRAS signaling at different levels including (1) inhibit RAS membrane association and (2) inhibit downstream KRAS effectors. The present chapter highlights the existing approaches in the management of KRAS-driven cancers by targeting RAS, and also discusses the potential drug candidates on this horizon.

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Acknowledgments

We gratefully acknowledge the Fundamental Research Grant Scheme grants (FRGS/1/2014/SKK01/MUSM/03/2) from the Ministry of Higher Education Malaysia for financial support on our research on KRAS mutation as a drug target in cancers.

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Authors and Affiliations

  1. School of Science, Monash University Malaysia, Subang Jaya, Selangor, Malaysia

    Shu-Kee Eng & Wai-Leng Lee

  2. Biomedical Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya, Selangor, Malaysia

    Teng Hern Tan Loh & Bey-Hing Goh

  3. Biofunctional Molecule Exploratory Research Group (BMEX), School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia

    Teng Hern Tan Loh & Bey-Hing Goh

  4. Novel Bacteria and Drug Discovery Research Group (NBDD), School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia

    Teng Hern Tan Loh & Bey-Hing Goh

  5. Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes, Health and Well-Being Cluster, Global Asia in the 21st Century Platform, Monash University Malaysia, Subang Jaya, Selangor, Malaysia

    Bey-Hing Goh

  6. Center of Health Outcomes Research and Therapeutic Safety, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand

    Bey-Hing Goh

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  1. Shu-Kee Eng
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  2. Teng Hern Tan Loh
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  4. Wai-Leng Lee
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Correspondence to Wai-Leng Lee .

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  1. Department of Botany, Gandhi Faiz-e-Aam College, Shahjahanpur, Uttar Pradesh, India

    Mohd Sayeed Akhtar

  2. Department of Biotechnology, East West First Grade College of Science, Bengaluru, Karnataka, India

    Mallappa Kumara Swamy

  3. Department of Crop Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

    Uma Rani Sinniah

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Eng, SK., Loh, T.H.T., Goh, BH., Lee, WL. (2019). KRAS as Potential Target in Colorectal Cancer Therapy. In: Akhtar, M., Swamy, M., Sinniah, U. (eds) Natural Bio-active Compounds. Springer, Singapore. https://doi.org/10.1007/978-981-13-7154-7_12

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