Integrins as attractive targets for cancer therapeutics

Abstract

Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological processes. These molecules facilitate cell-extracellular matrix and cell-cell interactions, and they have been implicated in fibrosis, inflammation, thrombosis, and tumor metastasis. The role of integrins in tumor progression makes them promising targets for cancer treatment, and certain integrin antagonists, such as antibodies and synthetic peptides, have been effectively utilized in the clinic for cancer therapy. Here, we discuss the evidence and knowledge on the contribution of integrins to cancer biology. Furthermore, we summarize the clinical attempts targeting this family in anti-cancer therapy development.

Keywords: ADAMs, adisintegrin and metalloproteases; AJ, adherens junctions; Antagonists; CAFs, cancer-associated fibroblasts; CAR, chimeric antigen receptor; CRC, colorectal cancer; CSC, cancer stem cell; Clinical trial; ECM, extracellular matrix; EGFR, epidermal growth factor receptor; EMT, epithelial–mesenchymal transition; ERK, extracellular regulated kinase; Extracellular matrix; FAK, focal adhesion kinase; FDA, U.S. Food and Drug Administration; HIF-1α, hypoxia-inducible factor-1α; HUVECs, human umbilical vein endothelial cells; ICAMs, intercellular adhesion molecules; IGFR, insulin-like growth factor receptor; IMD, integrin-mediated death; Integrins; JNK, c-Jun N-terminal kinase 16; MAPK, mitogen-activated protein kinase; MMP2, matrix metalloprotease 2; NF-κB, nuclear factor-κB; NSCLC, non-small cell lung cancer; PDGFR, platelet-derived growth factor receptor; PI3K, phosphatidylinositol 3-kinase; RGD, Arg-Gly-Asp; RTKs, receptor tyrosine kinases; SAPKs, stress-activated MAP kinases; SDF-1, stromal cell-derived factor-1; SH2, Src homology 2; STAT3, signal transducer and activator of transcription 3; TCGA, The Cancer Genome Atlas; TICs, tumor initiating cells; TNF, tumor necrosis factor; Targeted drug; Tumor progression; VCAMs, vascular cell adhesion molecules; VEGFR, vascular endothelial growth factor receptor; mAb, monoclonal antibodies; sdCAR-T, switchable dual-receptor CAR-engineered T; siRNA, small interference RNA; uPA, urokinase-type plasminogen activator.