Integrins in cancer: Emerging mechanisms and therapeutic opportunities

Identifying the prognosis implication, immunotherapy response prediction value, and potential targeted compound inhibitors of integrin subunit α3 (ITGA3) in human cancers

“…Activated CAFs could promote angiogenesis, cancer progression, invasion, and metastasis, and cause ECM remodeling [ 46 ]. Moreover, as vital surface adhesion receptors mediate interactions between the ECM, the regulation of integrins in the ECM may be closely related to the above processes [ 4 ]. In addition, previous studies have found that Tregs and MDSCs could help tumors avoid the response to immunotherapy and promote tumor immunosuppression [ [47] , [48] , [49] , [50] ].…”

“…Integrins are cell surface adhesion receptors that mediate the interactions between extracellular matrix (ECM) and cells, playing a crucial role in cell migration and maintenance of tissue homeostasis [ 4 ]. The integrin family consists of 18 α subunits and 8 β subunits, which could combine in various combinations to form 24 distinct integrins [ 5 ].…”

“…The integrin family consists of 18 α subunits and 8 β subunits, which could combine in various combinations to form 24 distinct integrins [ 5 ]. Recently, dysregulated integrin signaling, which is overly activated in the tumor microenvironment, and could positively impact tumor immunobiology, has gradually been taken seriously [ 4 , 6 ]. Integrins have emerged as promising targets for the development of cancer treatment [ 7 , 8 ].…”

Targets of tumor microenvironment for potential drug development

“…They are transmembrane cell adhesion receptors that facilitate cell–cell and cell–ECM adhesion. Multiple integrin‐targeting drugs are being tested in clinical trials, 246,247 including antiangiotide which targets αvβ3 integrin, 248 CEND‐1 peptide which targets αvβ5 integrin, 249 small molecule 7HP‐349 which targets αLβ2/α4β1, 250 and HYD‐PEP06 which targets pan‐αv 251 . Osteopontin (OPN), a matricellular phosphoglycoprotein known for its binding capacity with integrins to promote cell–ECM interactions, is overexpressed in diverse cancer types and participates in tumor proliferation, metastasis, angiogenesis, and resistance to chemotherapy 252 .…”

The Role of Snake Venom Disintegrins in Angiogenesis

“…Dysregulation of integrin activity has been implicated in numerous pathological conditions, such as cancer, inflammation, and thrombosis [ 38 , 39 ]. Consequently, inhibiting integrin binding has emerged as a promising therapeutic strategy [ 40 , 41 ].…”