Tissue platelet derived-growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancer

Seymour, Lesley; Dajee, D.; Wr, Bezwoda

doi:10.1007/bf00665802

Cited by 86 publications

(85 citation statements)

References 9 publications

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“…The median number of treatment cycles was three (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] in the 20 evaluable patients ( Table 2). Fifteen (75%) discontinued treatment because of progressive disease and five (25%) discontinued treatment because of adverse events, including: grade 3 headache (n ϭ 1), grade 3 transaminitis (n ϭ 1), grade 2 dyspepsia and weight loss (n ϭ 1), grade 3 headache, hypertension, and chest pain (n ϭ 1), and grade 3 gastrointestinal hemorrhage (n ϭ 1).…”

Section: Treatmentmentioning

confidence: 99%

“…A number of key proangiogenic factors, including vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) [4,5] and the class III receptor tyrosine kinases platelet-derived growth factor receptor (PDGFR) [6,7] and stem cell factor receptor (KIT), are overexpressed in breast cancer [8 -10]. Many of these are associated with a poor prognosis [11][12][13][14] and a poor response to systemic chemotherapy in advanced breast cancer patients [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium

et al. 2010

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Purpose. Angiogenesis is an important hallmark of breast cancer growth and progression. Pazopanib, an oral small molecule inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and KIT, has activity across a range of solid tumors. We evaluated the activity of singleagent pazopanib in recurrent or metastatic breast cancer (MBC).Patients and Methods. Patients with recurrent breast cancer or MBC, treated with up to two prior lines of chemotherapy, were eligible to receive pazopanib, 800 mg daily until progression. The primary endpoint was the objective response rate as measured by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included time to progression, the stable disease rate, and toxicity. Using a two-stage design, confirmed response in three of 18 patients was required to proceed to stage 2.Results. Twenty evaluable patients were treated, with a median age of 56 years; 70% were estrogen receptor positive, all were human epidermal growth factor receptor 2 negative. The majority had one or two prior lines of chemotherapy. One patient (5%) had a partial response, 11 (55%) had stable disease

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Section: Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium

et al. 2010

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“…For example, PDGF, which plays an important role in many human malignancies (Heldin, 1992) exists in three isoforms (homodimers PDGF-AA and PDGF-BB and heterodimer PDGF-AB) and exerts its biological eects via speci®c binding to PDGF receptors (PDGFRs) (Hart et al, 1988). Overexpression of PDGFR is seen in certain breast (Seymour et al, 1993) and ovarian (Henriksen et al, 1993) carcinomas as well as high serum levels of PDGF. Furthermore, elevated levels of PDGF and PDGFR in breast cancer patients correlate with poor response to chemotherapy and shorter survival times (Seymour et al, 1993).…”

Section: Receptor Tyrosine Kinases As Targets For Cancer Chemotherapymentioning

confidence: 99%

“…Overexpression of PDGFR is seen in certain breast (Seymour et al, 1993) and ovarian (Henriksen et al, 1993) carcinomas as well as high serum levels of PDGF. Furthermore, elevated levels of PDGF and PDGFR in breast cancer patients correlate with poor response to chemotherapy and shorter survival times (Seymour et al, 1993). The design of PDGF antagonists that can inhibit ligand-induced receptor activation has been suggested as a route to new anti-cancer drugs (Fiona and William, 1994).…”

Section: Receptor Tyrosine Kinases As Targets For Cancer Chemotherapymentioning

confidence: 99%

Design of growth factor antagonists with antiangiogenic and antitumor properties

Sebti

Hamilton

2000

Oncogene

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This review describes our recent eorts in the development of novel therapies for cancer. Our primary approach is to design synthetic agents that antagonize the function of growth factors that are critically involved in oncogenesis and angiogenesis. We achieve this by designing synthetic molecules that can recognize the exterior surface of the growth factor and so block the interaction with its receptor tyrosine kinase. A key step is the construction of synthetic agents that contain a large (4400A Ê 2 ) and functionalized surface area to recognize a complementary surface on the target growth factor. In the course of this work we have discovered a molecule, GFB-111, that binds to PDGF, prevents it from binding to its receptor tyrosine kinase, blocks PDGF-induced receptor autophosphorylation, activation of Erk1 and Erk2 kinases and DNA synthesis. The binding anity for PDGF is high (IC 50 =250 nM) and selective over EGF, IGF-1, aFGF, bFGF and HRGb. In nude mouse models GFB-111 also shows signi®cant inhibition of tumor growth and angiogenesis. Oncogene (2000) 19, 6566 ± 6573.

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“…4 PDGF and PDGF receptor (PDGF-R) are expressed in many types of human neoplasm, including neoplasm of the prostate, 5 lung, 6 colon 7 and breast. 8,9 PDGF is a dimeric protein of the following molecular variants: PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC and PDGF-DD. 10 The a-receptor binds all possible forms of PDGF except PDGF-DD, whereas PDGF-Rb preferentially binds PDGF-BB.…”

mentioning

confidence: 99%

Anti‐stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model

Sumida

Kitadai

Shinagawa

et al. 2011

Intl Journal of Cancer

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Recent studies have revealed that platelet-derived growth factor (PDGF) plays a role in promoting progressive tumor growth in several organs; however, whether PDGF plays such a role in gastric carcinoma is undetermined. We examined whether inhibition of PDGF receptor (PDGF-R) tyrosine kinase signaling by imatinib affects tumor growth and metastasis in an orthotopic nude mouse model of human gastric carcinoma. TMK-1 human gastric carcinoma cells were injected into the gastric wall of nude mice. Groups of mice (n 5 10 each) received sterile water (control), low-dose imatinib (50 mg/kg/day), high-dose imatinib (200 mg/kg/day), cancer chemotherapeutic agent irinotecan (5 mg/kg/week), or imatinib (50 mg/kg/day or 200 mg/kg/day) and irinotecan (5 mg/kg/week) in combination for 28 days. Tumor growth and metastasis were assessed. Resected tumors were analyzed immunohistochemically. Carcinoma-associated fibroblasts, pericytes and lymphatic endothelial cells in stroma expressed high levels of PDGF-R; carcinoma cells did not. Treatment with imatinib alone did not inhibit tumor growth and metastasis; however, treatment with irinotecan alone or combined with imatinib significantly inhibited tumor growth. Only treatment with high-dose imatinib and irinotecan in combination inhibited lymph node and peritoneal metastases. Immunohistochemically, only imatinib alone or in combination with irinotecan was shown to significantly decrease the stromal reaction, microvessel area and pericyte coverage of tumor microvessels. These effects were marked with high-dose imatinib. In conclusion, administration of PDGF-R tyrosine kinase inhibitor in combination with irinotecan appears to impair the progressive growth of gastric carcinoma by blockade of PDGF-R signaling pathways in stromal cells.Recent studies in tumor biology have shown that tumor growth and metastasis are determined not only by cancer cells, but also by a variety of stromal cells. The stroma constitutes a large part of most solid tumors, and the cancer-stromal cell interaction contributes functionally to tumor growth and metastasis.

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Tissue platelet derived-growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancer

Cited by 86 publications

References 9 publications

A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium

A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium

Design of growth factor antagonists with antiangiogenic and antitumor properties

Anti‐stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model

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