Reprogramming tumor-associated macrophages: The role of MEK-STAT3 inhibition in lung cancer

Sushama Rawat; Ehssan Moglad; Muhammad Afzal; Ahsas Goyal; R Roopashree; Pooja Bansal; Shivang Mishra; G V Siva Prasad; Atreyi Pramanik; Sami I Alzarea; Haider Ali; Mohd Imran; Abida

doi:10.1016/j.prp.2024.155748

Reprogramming tumor-associated macrophages: The role of MEK-STAT3 inhibition in lung cancer

Pathol Res Pract. 2024 Nov 28:265:155748. doi: 10.1016/j.prp.2024.155748. Online ahead of print.

Authors

Sushama Rawat¹, Ehssan Moglad², Muhammad Afzal³, Ahsas Goyal⁴, R Roopashree⁵, Pooja Bansal⁶, Shivang Mishra⁷, G V Siva Prasad⁸, Atreyi Pramanik⁹, Sami I Alzarea¹⁰, Haider Ali¹¹, Mohd Imran¹², Abida¹²

Affiliations

¹ Department of Biotechnology, Graphic Era (Deemed to be University), Clement Town, Dehradun 248002, India. Electronic address: rawatpharma.s@outlook.com.
² Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia.
³ Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, PO Box 6231, Jeddah 21442, Saudi Arabia.
⁴ Institute of Pharmaceutical Research, GLA University, Mathura, UP, India.
⁵ Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
⁶ Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India.
⁷ NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India.
⁸ Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh 531162, India.
⁹ School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India.
¹⁰ Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf 72341, Saudi Arabia.
¹¹ Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
¹² Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia; Center for Health Research, Northern Border University, Arar, Saudi Arabia.

PMID: 39616977
DOI: 10.1016/j.prp.2024.155748

Abstract

Tumor-associated macrophages (TAMs) crucially contribute to lung cancer's advancement and escape from the immune system. TAMs, particularly the M2 phenotype, promote an immunosuppressive microenvironment, facilitating tumor growth and metastasis. The MEK-STAT3 signalling pathway is a critical mediator in this process, driving TAM reprogramming and contributing to lung cancer's resistance to treatment. Inhibiting the MEK and STAT3 pathways disrupts key cancer-promoting mechanisms, including immune evasion, angiogenesis, and metastasis. Preclinical studies have demonstrated the effectiveness of MEK inhibitors, such as trametinib and selumetinib, in synergistic therapies for NSCLC, particularly in modulating the tumor microenvironment. We analyse the present understanding of approaches that can transform TAMs via the inhibition of MEK-STAT3 with either solo or combined treatments in lung cancer therapy.

Keywords: Apoptosis; Lung cancer; MEK; Metastasis; NSCLC; STAT3; TAMs.

Publication types

Review