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 language | English (US) |
|---|---|
| Pages (from-to) | 30146-30162 |
| Number of pages | 17 |
| Journal | Oncotarget |
| Volume | 9 |
| Issue number | 53 |
| DOIs | |
| State | Published - Jul 10 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Identification of integrin drug targets for 17 solid tumor types
AU - Arun, Adith S.
AU - Tepper, Clifford G
AU - Lam, Kit
PY - 2018/7/10
Y1 - 2018/7/10
N2 - 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.
AB - 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.
KW - Computational genomics
KW - Integrins
KW - Precision medicine
KW - Therapeutic target selection
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85049754071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049754071&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.25731
DO - 10.18632/oncotarget.25731
M3 - Article
AN - SCOPUS:85049754071
VL - 9
SP - 30146
EP - 30162
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 53
ER -