The Role of the Toll-like Receptor 2 and the cGAS-STING Pathways in Breast Cancer: Friends or Foes?

Author:

Cossu Chiara1,Di Lorenzo Antonino1ORCID,Fiorilla Irene2,Todesco Alberto Maria2,Audrito Valentina2ORCID,Conti Laura1ORCID

Affiliation:

1. Department of Molecular Biotechnology and Health Sciences–Molecular Biotechnology Center “Guido Tarone”, University of Turin, Piazza Nizza 44, 10126 Turin, Italy

2. Department of Science and Technological Innovation (DISIT), University of Eastern Piedmont, 15121 Alessandria, Italy

Abstract

Breast cancer stands as a primary malignancy among women, ranking second in global cancer-related deaths. Despite treatment advancements, many patients progress to metastatic stages, posing a significant therapeutic challenge. Current therapies primarily target cancer cells, overlooking their intricate interactions with the tumor microenvironment (TME) that fuel progression and treatment resistance. Dysregulated innate immunity in breast cancer triggers chronic inflammation, fostering cancer development and therapy resistance. Innate immune pattern recognition receptors (PRRs) have emerged as crucial regulators of the immune response as well as of several immune-mediated or cancer cell-intrinsic mechanisms that either inhibit or promote tumor progression. In particular, several studies showed that the Toll-like receptor 2 (TLR2) and the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathways play a central role in breast cancer progression. In this review, we present a comprehensive overview of the role of TLR2 and STING in breast cancer, and we explore the potential to target these PRRs for drug development. This information will significantly impact the scientific discussion on the use of PRR agonists or inhibitors in cancer therapy, opening up new and promising avenues for breast cancer treatment.

Funder

AIRC—Associazione Italiana di Ricerca sul Cancro

Fondazione CRT

University of Turin

Associazione Italiana di Ricerca sul Cancro

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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