Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities

Author:

Tiwari Aniket1,Kumari Beauty1ORCID,Nandagopal Srividhya2,Mishra Amit1ORCID,Shukla Kamla Kant2ORCID,Kumar Ashok3,Dutt Naveen4,Ahirwar Dinesh Kumar1ORCID

Affiliation:

1. Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur 342030, Rajasthan, India

2. Department of Biochemistry, All India Institute of Medical Sciences Jodhpur, Jodhpur 342005, Rajasthan, India

3. Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal 462020, Madhya Pradesh, India

4. Department of Pulmonary Medicine, All India Institute of Medical Sciences Jodhpur, Jodhpur 342005, Rajasthan, India

Abstract

SCLC is refractory to conventional therapies; targeted therapies and immunological checkpoint inhibitor (ICI) molecules have prolonged survival only marginally. In addition, ICIs help only a subgroup of SCLC patients. Different types of kinases play pivotal roles in therapeutics-driven cellular functions. Therefore, there is a significant need to understand the roles of kinases in regulating therapeutic responses, acknowledge the existing knowledge gaps, and discuss future directions for improved therapeutics for recalcitrant SCLC. Here, we extensively review the effect of dysregulated kinases in SCLC. We further discuss the pharmacological inhibitors of kinases used in targeted therapies for recalcitrant SCLC. We also describe the role of kinases in the ICI-mediated activation of antitumor immune responses. Finally, we summarize the clinical trials evaluating the potential of kinase inhibitors and ICIs. This review overviews dysregulated kinases in SCLC and summarizes their potential as targeted therapeutic agents. We also discuss their clinical efficacy in enhancing anticancer responses mediated by ICIs.

Funder

United States Department of Defense

Publisher

MDPI AG

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