Fig. 1

Main mechanisms involved in drug resistance. Upon treatment with chemotherapeutic drugs, breast cancer cells can develop chemoresistance by: inducing drug efflux via the ATP-binding cassette (ABC) transporters (1), enhancing DNA repair through homologous recombination (HR) and nonhomologous end joining (NHEJ) pathways (2), reducing activation of intrinsic and extrinsic apoptosis pathways (3), activating prosurvival signaling pathways (4), increasing the expression of hypoxia-inducible factor (HIF) in a hypoxic microenvironment (5), reprogramming metabolism (6), remodeling the tumor microenvironment (7). CSF, colony-stimulating factor; IL, interleukin; TGF, transforming growth factor; CXCL, C–X–C motif chemokine ligand; miRNA, microRNA; TNF, tumor necrosis factor; TNFR, tumor necrosis receptor; ALDH, aldehyde dehydrogenase; CAFs, cancer-associated fibroblasts; TAMs, tumor-associated macrophages; BCSCs, breast cancer stem cells; EVs, extracellular vesicles; MSCs, mesenchymal stem cells; ECM, extracellular matrix; ABC-transporters, ATP-binding cassette transporters; HR, hormone receptors; NHEJ, nonhomologous end joining; HIF, hypoxia-inducible factors; Bcl, B-cell lymphoma; JAK, Janus kinase; STAT, signal transducer and activator of transcription; PI3K, phosphoinositide 3-LKinase; AKT, protein kinase B; mTOR, mammalian target of rapamycin; NF-kB, nuclear factor-kappa B; cAMP, cyclic adenosine 3′,5′-monophosphate; PKA, protein kinase A. Figure created with PowerPoint by Microsoft Office 365