Current perspectives of cancer-associated fibroblast in therapeutic resistance: potential mechanism and future strategy

Abstract

The goal of cancer eradication has been overshadowed despite the continuous improvement in research and generation of novel cancer therapeutic drugs. One of the undeniable existing problems is drug resistance due to which the paradigm of killing all cancer cells is ineffective. Tumor microenvironment plays a crucial role in inducing drug resistance besides cancer development and progression. Recently, many efforts have been devoted to understand the role of tumor microenvironment in cancer drug resistance as it provides the shelter, nutrition, and paracrine niche for cancer cells. Cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, reside in symbiotic relationship with cancer cells, supporting them to survive from cancer drugs. The present review summarizes the recent understandings in the role of CAFs in drug resistance in various tumors. Acknowledging the fact that drug resistance depends not only upon cancer cells but also upon the microenvironment niche could guide us to formulate novel cancer drugs and provide the optimal cancer treatment.

Keywords: Cancer-associated fibroblast; Drug resistance.

Fig. 1

Heterogeneous origin of CAFs and its markers. Cancer-associated fibroblasts are originated from various sources, which are in quiescent state and convert into CAFs after communicating with malignant cells and express different markers differentiating from its progenitor state

Fig. 2

The dual nature of CAFs. Two distinct subpopulation of CAFs that are based on its secretory function and expression markers and play the subsequent role in tumor microenvironment

Fig. 3

Roles of CAFs in drug resistance. CAFs play important role in cancer drug resistance via secretion of different factors and modulation of tumor microenvironment resulting reduction of drug efficacy or activation of cancer cells by alternating pathway