The Role of Cancer-associated Fibroblasts in the Microenvironment of Invasive Ductal Carcinoma (IDC) Breast Cancer
Habib Olaniran Kolawole
Faculty of Dentistry, College of Medicine, University of Ibadan, Oyo State, Nigeria.
Enibokun Theresa Orobator
University of Edinburgh, United Kingdom.
Blessing Imade
Department of Medical Laboratory Science, University of Benin, Benin City, Edo State, Nigeria.
Victor Damilare Oladele
Department of Biomedical Science, University of Salford, England.
Ezema Izuchukwu Gerald
University College Hospital, Ibadan, Nigeria.
Kamsiyochukwu Anita Ezeani
Department of Medicine, University of Nigeria, Enugu, Nigeria.
Daniel Ebubechi Obasi
College of Medicine, University of Ibadan, Oyo State, Nigeria.
Adegbesan Abiodun Christopher
Department of Global Health, African Cancer Institute, Stellenbosch University, Cape Town, South Africa.
Peter Bemigho Adewoyin
Department of Medicine and Surgery, Obafemi Awolowo University, Osun State, Nigeria.
Lawrence John Ajutor
*
Faculty of Dentistry, College of Medicine, University of Ibadan, Oyo State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
There has been an increase in the amount of studies focusing on the relevance of tumour microenvironment (TME) in metastasis of breast cancer. Cancer-associated fibroblasts (CAFs) is one of the most abundant cells found in the TME that play key roles in the metastasis of cancers particularly in invasive ductal carcinoma (IDC), a common type of breast cancer. In a bid to constantly find novel treatments to address limited number of therapy that are currently available, CAFs have emerged as a target for many researches. This review aims to explore the multifaceted role of CAFs in IDC progression, highlighting their involvement in tumour growth, angiogenesis, epithelial-to-mesenchymal transition (EMT), immune modulation, and drug resistance. Additional focus was also placed on potential therapeutic benefit of targeting CAFs. A comprehensive review of recent studies on the subject CAF biology, CAF interactions within the TME, and existing therapeutic approaches targeting CAFs in IDC was conducted. Findings show that CAFs are crucial to the dynamics of the TME and they influence tumour progression. CAFs facilitate tumour progression through various mechanisms, some of which are: secretion of pro-tumorigenic factors and ECM remodelling. CAFs also play a part in suppression of immune responses. CAF-targeted drugs have shown promising results in treatment for patients. Mechanism of CAF-targeting drugs is through inhibition of TGF-β signalling and reprogramming of CAFs. However, challenges of CAF heterogeneity and off-target effects will have to be addressed. Interestingly, CAF being a key mediator of the TME in cancer also present potential diagnostic and prognostic value to assesses IDC progression. Targeting CAFs offers a promising approach for IDC diagnosis and treatment, although more research is needed to refine strategies for selective CAF targeting and overcoming therapeutic challenges.
Keywords: Invasive ductal carcinoma, cancer-associated fibroblasts, CAFs in IDC, tumour microenvironment, TGF-β signalling