Abstract
Cancer is a complex disease in which erratic cellular signaling leads to uncontrolled growth and proliferation. Several drugs and therapies have been developed to control these signaling perturbations so as to kill the tumor cells. Despite these advances, cancer is a compounding global health problem made severe by the ever-increasing drug resistance. The number of new drugs approved is hopelessly outpaced by the instances of drug resistance and relapses. Posttranslational modifications (PTMs) are emerging as a hidden regulatory layer controlling metabolism and homeostasis. Drugs usually target PTMs to kill tumor cells. PTMs are also exploited by cancer cells to maintain their growth and survival by rewiring survival signaling pathways that can introduce drug resistance, both intrinsic and acquired. In this chapter, we discuss major known resistance mechanisms in cancer, exemplify how PTMs are involved in those, and attract the attention of drug discovery community toward this regulatory mechanism. A thorough understanding of the role of PTMs in these signaling changes can play a significant role in solving the drug resistance problem. We believe that combination therapies exploiting the PTMs may have a better chance of treating cancer and averting the intractable problems of drug resistance and cancer relapse.
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Acknowledgement
AKY is supported by the Innovative Young Biotechnologist Award (IYBA) and MK is supported by the IYBA Junior Research Fellowship (IYBA-JRF) from the Department of Biotechnology, India. Suruchi Aggarwal is supported by the Senior Research Fellowship (SRF) from the Indian Council of Medical Research (ICMR), India. AKY and Shailendra Asthana also acknowledge DDRC-SFC grant from the Department of Biotechnology, India. Authors thank Dr. Kanury V.S. Rao for critical comments on the manuscript.
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Aggarwal, S., Kandpal, M., Asthana, S., Yadav, A.K. (2017). Perturbed Signaling and Role of Posttranslational Modifications in Cancer Drug Resistance. In: Arora, G., Sajid, A., Kalia, V. (eds) Drug Resistance in Bacteria, Fungi, Malaria, and Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-48683-3_22
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