Targeting the heparin-binding epidermal growth factor-like growth factor in ovarian cancer therapy

Tsujioka, Hiroshi; Yotsumoto, Fusanori; Hikita, Shoko; Ueda, Taeko; Kuroki, Masahide; Miyamoto, Shingo

doi:10.1097/gco.0b013e3283409c91

Cited by 30 publications

(25 citation statements)

References 50 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although no antibody to an EGF-like molecule has so far been approved for clinical applications, it is notable that an HB-EGF inhibitor (CRM197) is active both as a single agent and in combination with other anticancer agents (Sanui et al , 2010; Tsujioka et al , 2011), and bevacizumab, a therapeutic antibody used to treat colorectal and other tumors, can intercept the vascular endothelial growth factor (VEGF). In contrast to the VEGF family, the greater multiplicity of the EGF family ligands calls for a more general approach, such as the “tailor made” strategy we developed (Lindzen et al , 2010).…”

Section: Discussionmentioning

confidence: 99%

A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis

et al. 2011

View full text Add to dashboard Cite

EGF-like growth factors control tumor progression, as well as evasion from the toxic effects of chemotherapy. Accordingly, antibodies targeting the cognate receptors, such as EGFR/ErbB-1 and the co-receptor HER2/ErbB-2, are widely used to treat cancer patients, but agents that target the EGF-like growth factors are not available. To circumvent the existence of 11 distinct ErbB ligands, we constructed a soluble fusion protein (hereinafter: TRAP-Fc) comprising truncated extracellular domains of EGFR/ErbB-1 and ErbB-4. The recombinant TRAP-Fc retained high affinity ligand binding to EGF-like growth factors and partially inhibited growth of a variety of cultured tumor cells. Consistently, TRAP-Fc displayed an inhibitory effect in xenograft models of human cancer, as well as synergy with chemotherapy. Additionally, TRAP-Fc inhibited invasive growth of mammary tumor cells and reduced their metastatic seeding in the lungs of animals. Taken together, the activities displayed by TRAP-Fc reinforce critical roles of EGF-like growth factors in tumor progression, and they warrant further tests of TRAP-Fc in pre-clinical models.

show abstract

Section: Discussionmentioning

confidence: 99%

A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Previous phase II clinical studies with imatinib and gefitinib in patients with refractory or recurrent EOC suggested that although these agents have marginal benefits as monotherapies in EOC, their ability to modulate molecular targets (e.g., EGFR, c-Kit, PDGFR, ERK, AKT) and demonstrate proof of concept corroborates their applicability in combinatorial molecular therapeutics [198, 199]. A number of reports have reinforced the notion that inhibition of a single transduction pathway may be insufficient since activation of alternative signaling cascades may conceal efficacy, and that it would be more advantageous to target integrated cancer signals, for example, VEGFR- and EGFR-interdependent pathways [170] and heparin-binding epidermal growth factor-like growth factor (HB-EGF) [200, 201]. Remarkably also, the mammalian target of rapamycin (mTOR) is a central intracellular kinase that not only orchestrates proliferation, survival, and angiogenic pathways, but has also been linked to resistance to EGFR antagonists, and thus mTOR inhibition could be explored to interfere with tumor growth and expansion at multiple levels [4, 83, 84, 92, 159, 170, 202–205].…”

Section: Ovarian Cancer Biomarkers and Cellsignaling Pathwaysmentioning

confidence: 90%

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

Hiss

2012

Journal of Oncology

View full text Add to dashboard Cite

The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discovery is devoted to identifying diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and reliability of such biomarkers may be complicated by mutations in the BRCA1 or BRCA2 genes, diverse genetic risk factors, unidentified initiation and progression elements, molecular tumor heterogeneity and disease staging. There is thus a dire need to expand existing ovarian cancer therapies with broad-spectrum and individualized molecular targeted approaches. The aim of this review is to profile recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into more efficacious targeted treatment rationales.

show abstract

“…IL-6 and IL-8 are also important contributors to ovarian cancer angiogenesis, as demonstrated in preclinical models (34 -36). A few preclinical studies demonstrated the efficacy of different HB-EGF inhibitors in the reduction of ovarian tumor growth when administered alone or in combination with paclitaxel (37,38). Thus modulation of expression of multiple angiogenic cytokines through HB-EGF represents an attractive opportunity to target ovarian tumor angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Ovarian Cancer Cell Heparan Sulfate 6-O-Sulfotransferases Regulate an Angiogenic Program Induced by Heparin-binding Epidermal Growth Factor (EGF)-like Growth Factor/EGF Receptor Signaling

Cole

Rushton

Jayson³

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Numerous angiogenic growth factors depend on heparan sulfate for their activity. Results: Heparan sulfate 6-O-sulfotransferases induce angiogenesis through HB-EGF/EGFR signaling and angiogenic cytokine expression in ovarian cancer cells. Conclusion: Ovarian cancer cell 6-O-sulfation levels influence angiogenic responses. Significance: HS6ST inhibitors and HS mimetics should be explored in the development of new anti-angiogenic agents.

show abstract

Targeting the heparin-binding epidermal growth factor-like growth factor in ovarian cancer therapy

Cited by 30 publications

References 50 publications

A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis

A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

Ovarian Cancer Cell Heparan Sulfate 6-O-Sulfotransferases Regulate an Angiogenic Program Induced by Heparin-binding Epidermal Growth Factor (EGF)-like Growth Factor/EGF Receptor Signaling

Contact Info

Product

Resources

About