Identification of integrin drug targets for 17 solid tumor types

Adith S. Arun, Clifford G Tepper, Kit Lam

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Integrins are contributors to remodeling of the extracellular matrix and cell migration. Integrins participate in the assembly of the actin cytoskeleton, regulate growth factor signaling pathways, cell proliferation, and control cell motility. In solid tumors, integrins are involved in promoting metastasis to distant sites, and angiogenesis. Integrins are a key target in cancer therapy and imaging. Integrin antagonists have proven successful in halting invasion and migration of tumors. Overexpressed integrins are prime anti-cancer drug targets. To streamline the development of specific integrin cancer therapeutics, we curated data to predict which integrin heterodimers are pausible therapeutic targets against 17 different solid tumors. Computational analysis of The Cancer Genome Atlas (TCGA) gene expression data revealed a set of integrin targets that are differentially expressed in tumors. Filtered by FPKM (Fragments Per Kilobase of transcript per Million mapped reads) expression level, overexpressed subunits were paired into heterodimeric protein targets. By comparing the RNA-seq differential expression results with immunohistochemistry (IHC) data, overexpressed integrin subunits were validated. Biologics and small molecule drug compounds against these identified overexpressed subunits and heterodimeric receptors are potential therapeutics against these cancers. In addition, high-affinity and high-specificity ligands against these integrins can serve as efficient vehicles for delivery of cancer drugs, nanotherapeutics, or imaging probes against cancer.

Original languageEnglish (US)
Pages (from-to)30146-30162
Number of pages17
JournalOncotarget
Volume9
Issue number53
DOIs
StatePublished - Jul 10 2018

Fingerprint

Integrins
Pharmaceutical Preparations
Neoplasms
Cell Movement
Atlases
Therapeutics
Biological Products
Actin Cytoskeleton
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Immunohistochemistry
Cell Proliferation
Genome
RNA
Neoplasm Metastasis
Ligands
Gene Expression

Keywords

  • Computational genomics
  • Integrins
  • Precision medicine
  • Therapeutic target selection
  • Transcriptomics

ASJC Scopus subject areas

  • Oncology

Cite this

Identification of integrin drug targets for 17 solid tumor types. / Arun, Adith S.; Tepper, Clifford G; Lam, Kit.

In: Oncotarget, Vol. 9, No. 53, 10.07.2018, p. 30146-30162.

Research output: Contribution to journalArticle

Arun, Adith S. ; Tepper, Clifford G ; Lam, Kit. / Identification of integrin drug targets for 17 solid tumor types. In: Oncotarget. 2018 ; Vol. 9, No. 53. pp. 30146-30162.
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