What about αvβ3 integrins in molecular imaging in oncology?

Debordeaux, F.; Chansel‐Debordeaux, Lucie; Pinaquy, Jean-Baptiste; Fernandez, Philippe; Schulz, Jürgen

doi:10.1016/j.nucmedbio.2018.04.006

Cited by 35 publications

(25 citation statements)

References 216 publications

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“…Integrin αvβ3 is broadly expressed in different types of cells such as endothelial cells, osteoclasts and blood cells. Notably, the expression of the receptor is high in tumors including activated tumor endothelial cells, glioblastomas, malignant melanomas, breast, lung, pancreatic and prostate carcinomas, but not in resting endothelial cells and normal organ systems [39,40,41,42,43]. Furthermore, integrin αvβ3, in association with vitronectin, has been found to facilitate the differentiation of prostate and breast cancer stem cells (CSCs) and subsequently promote tumor formation [44].…”

Section: Integrinsmentioning

confidence: 99%

Integrins, CAFs and Mechanical Forces in the Progression of Cancer

Jang

Beningo

2019

Cancers

116

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Cells respond to both chemical and mechanical cues present within their microenvironment. Various mechanical signals are detected by and transmitted to the cells through mechanoreceptors. These receptors often contact with the extracellular matrix (ECM), where the external signals are converted into a physiological response. Integrins are well-defined mechanoreceptors that physically connect the actomyosin cytoskeleton to the surrounding matrix and transduce signals. Families of α and β subunits can form a variety of heterodimers that have been implicated in cancer progression and differ among types of cancer. These heterodimers serve as the nexus of communication between the cells and the tumor microenvironment (TME). The TME is dynamic and composed of stromal cells, ECM and associated soluble factors. The most abundant stromal cells within the TME are cancer-associated fibroblasts (CAFs). Accumulating studies implicate CAFs in cancer development and metastasis through their remodeling of the ECM and release of large amounts of ECM proteins and soluble factors. Considering that the communication between cancer cells and CAFs, in large part, takes place through the ECM, the involvement of integrins in the crosstalk is significant. This review discusses the role of integrins, as the primary cell-ECM mechanoreceptors, in cancer progression, highlighting integrin-mediated mechanical communication between cancer cells and CAFs.

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Section: Integrinsmentioning

confidence: 99%

Integrins, CAFs and Mechanical Forces in the Progression of Cancer

Jang

Beningo

2019

Cancers

116

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“…Integrin αVβ3, α5β1, and αVβ6 have been explored for non-invasive tumor imaging purposes, using magnetic resonance imaging (MRI), positron emission tomography (PET), computer tomography (CT), and optical and ultrasound-based imaging techniques [9,196,197]. Their targeting is of great potential relevance for the early diagnosis, staging of disease, patient’s stratification, and therapeutic monitoring [198]. The imaging of experimental tumors using modified αVβ3-binding Arg-Gly-Asp (RGD)-based peptides is a standard benchmark for the validation of tumor-targeting approaches [28].…”

Section: Targeting Integrins In Cancermentioning

confidence: 99%

Are Integrins Still Practicable Targets for Anti-Cancer Therapy?

Alday-Parejo

Stupp

Rüegg

2019

Cancers

134

127

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Correlative clinical evidence and experimental observations indicate that integrin adhesion receptors, in particular those of the αV family, are relevant to cancer cell features, including proliferation, survival, migration, invasion, and metastasis. In addition, integrins promote events in the tumor microenvironment that are critical for tumor progression and metastasis, including tumor angiogenesis, matrix remodeling, and the recruitment of immune and inflammatory cells. In spite of compelling preclinical results demonstrating that the inhibition of integrin αVβ3/αVβ5 and α5β1 has therapeutic potential, clinical trials with integrin inhibitors targeting those integrins have repeatedly failed to demonstrate therapeutic benefits in cancer patients. Here, we review emerging integrin functions and their proposed contribution to tumor progression, discuss preclinical evidence of therapeutic significance, revisit clinical trial results, and consider alternative approaches for their therapeutic targeting in oncology, including targeting integrins in the other cells of the tumor microenvironment, e.g., cancer-associated fibroblasts and immune/inflammatory cells. We conclude that integrins remain a valid target for cancer therapy; however, agents with better pharmacological properties, alternative models for their preclinical evaluation, and innovative combination strategies for clinical testing (e.g., together with immuno-oncology agents) are needed.

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“…Already some decades ago, great hope has been pinned on the "starvation" of tumours by inhibition of tumour-induced angiogenesis. One target structure involved in these processes is the integrin α v β 3 ; thus, a great variety of radiopharmaceuticals have been developed to target this receptor to allow treatment planning and control of corresponding antiangiogenic therapies (for a review, see, e.g., [4,184,185]). Most of these peptides are based on the cyclic pentapeptide structure c(RGDfV) developed by Kessler's group in 1991 [186].…”

Section: Integrinsmentioning

confidence: 99%

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

Rangger

Haubner

2020

Pharmaceuticals

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This review deals with the development of peptide-based radiopharmaceuticals for the use with positron emission tomography and peptide receptor radiotherapy. It discusses the pros and cons of this class of radiopharmaceuticals as well as the different labelling strategies, and summarises approaches to optimise metabolic stability. Additionally, it presents different target structures and addresses corresponding tracers, which are already used in clinical routine or are being investigated in clinical trials.

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What about αvβ3 integrins in molecular imaging in oncology?

Cited by 35 publications

References 216 publications

Integrins, CAFs and Mechanical Forces in the Progression of Cancer

Integrins, CAFs and Mechanical Forces in the Progression of Cancer

Are Integrins Still Practicable Targets for Anti-Cancer Therapy?

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

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