Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC

Pennell, Nathan A.; Lynch, Thomas J.

doi:10.1634/theoncologist.2008-0276

Cited by 87 publications

(59 citation statements)

References 88 publications

(127 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Preclinical and early clinical data (phase I and phase II trials) have supported combined inhibition of VEGFR and EGFR pathways in NSCLC (Pennell and Lynch, 2009). Activating EGFR mutations are predictive of response to EGFR inhibitors with reported response rates of upto 75%.…”

Section: Discussionmentioning

confidence: 99%

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

et al. 2009

View full text Add to dashboard Cite

Background: Blood-based biomarkers may be particularly useful for patient selection and prediction of treatment response for angiogenesis inhibitors. Circulating endothelial cells (CECs) and haematopoietic progenitor cells (HPCs) might have a role in tumour angiogenesis and in tumour growth. Measurement of CECs and HPCs in the blood of patients could be a simple, non-invasive way to monitor or predict responses to treatment. Methods: (VEGFR2 + ) CECs , (CD133 + ) HPCs, plasma vascular endothelial growth factor (VEGF) and erythropoietin were measured in blood from 25 non-small cell lung cancer (NSCLC) patients before and during treatment with sorafenib plus erlotinib (SO/ER). In order to assess the drug specificity of changes in CECs and HPCs, 18 patients treated with bevacizumab plus erlotinib (BV/ER) and 10 patients with erlotinib (ER) monotherapy were studied. Response was measured in all patient groups by Response Evaluation Criteria in Solid Tumors (RECIST). Results: At day 7, SO/ER-treated patients showed a three-fold increase in CECs ( P <0.0001) comparable to BV/ER-treated patients ( P <0.01), and the CECs did not change with erlotinib treatment ( P =0.8). At day 7, CD133 + /HPCs decreased with SO/ER treatment ( P <0.0001). HPC numbers did not change with either BV/ER or erlotinib. In SO/ER-treated patients pre-treatment CD133 + /HPCs were significantly lower in responders ( P =0.01) and pre-treatment CD133 + /HPC numbers lower than the median correlated with a longer time-to-progression (TTP) ( P =0.037). Conclusion: Pre-treatment CD133 + /HPCs are a promising candidate biomarker to further explore for use in selecting NSCLC patients who might benefit from SO/ER treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

et al. 2009

View full text Add to dashboard Cite

show abstract

“…It has been speculated that dual suppression may be critical for sustained suppression of tumor growth, especially because the EGFR and VEGFR pathways are linked and exhibit cross-talk. 25 In addition, vandetanib can also enhance the antiproliferative activity of selective EGFR inhibitors such as cetuximab, thereby potentiating suppression of EGFR signaling. 17 The present study confirmed that vandetanib, chronically administered over 2 weeks, slowed tumor growth in a colorectal tumor model, and, under the dosing conditions of this study, slowed tumor growth to a greater extent than CPT-11 alone and to a similar level to radiation alone.…”

Section: Discussionmentioning

confidence: 99%

Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model

Wachsberger

Burd

Ryan

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

“…Moreover, recent phase II/III clinical trials have confirmed an important clinical activity of ZD6474 in both NSCLC [8,11] and on RET-mutated MTC [12,13]. However, all these new small molecules demonstrated a higher activity when administered in combinations with chemotherapeutic drugs [14,15].…”

Section: Introductionmentioning

confidence: 98%

Antiproliferative and proapoptotic activity of CLM3, a novel multiple tyrosine kinase inhibitor, alone and in combination with SN-38 on endothelial and cancer cells

Bocci¹,

Fioravanti²,

Motta³

et al. 2011

Biochemical Pharmacology

View full text Add to dashboard Cite

Aims. To demonstrate the antiproliferative and pro-apoptotic activity of the novel pyrazolopyrimidine derivative multiple tyrosine kinase inhibitor CLM3, alone and in combination with SN-38 (the active metabolite of irinotecan), on endothelial and tumour cells and to show its mechanism of action.Methods. Proliferation and apoptotic assays were performed on microvascular endothelial (HMVECd) and lung (A549) and thyroid cancer (8305C, TT) cell lines exposed to CLM3 and to the simultaneous combination with SN38 for 72h. Cell-based phospho-VEGFR-2, phospho-EGFR and phospho-RET inhibition assays were performed and ERK1/2 and Akt phosphorylation were quantified by ELISA kits. Conclusions.The pyrazolopyrimidine derivative CLM3 demonstrated a highly significant and promising antiproliferative and proapoptotic activity, alone and in combination with SN-38, for activated endothelial and cancer cell cells. These effects are mainly due to its inhibition of phosphorylation of VEGFR-2, EGFR and RET tyrosine kinases and their related signalling pathways.

show abstract

Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC

Abstract: ABSTRACT

Cited by 87 publications

References 88 publications

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model

Antiproliferative and proapoptotic activity of CLM3, a novel multiple tyrosine kinase inhibitor, alone and in combination with SN-38 on endothelial and cancer cells

Contact Info

Product

Resources

About