Herceptin: From the Bench to the Clinic

Colomer, Ramón; Shamon, Lisa A.; Tsai, Miaw Sheue; Lupu, Ruth

doi:10.1081/cnv-100000074

Cited by 41 publications

(33 citation statements)

References 28 publications

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“…Overexpression of several growth factors, and growth factor receptors, has been demonstrated; for example, insulin-like growth factor I (IGF-1) and its receptors are overexpressed by breast cancer cells as well as erb-B2 receptors. The latter overexpression has led to the development of new therapeutic strategies that utilize specific blocking antibodies (Colomer et al, 2001). Fibroblast growth factor (FGF) and FGF receptor overexpression have also been described in breast cancer (Dickson et al, 2000), but as FGFs are ubiquitous molecules, this relative lack of specificity has hindered the development of FGF-related therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

“…This is best illustrated by the development of new therapeutic strategies based on the inhibition of the tyrosine kinase receptor Erb-B2, a member of the epidermal growth factor (EGF) receptor family. Erb-B2 overexpression in breast cancer cells has been demonstrated, and its specific inhibition with Herceptin, a truncated blocking antibody, has been successfully clinically trialed, to date with promising results (Colomer et al, 2001). However, the growth of breast cancer cells can be regulated by other growth factors that either stimulate or inhibit their proliferation, migration and differentiation, thus acting in concert to promote tumor growth and metastasis (Ethier, 1995;Le Bourhis et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Nerve growth factor overexpression and autocrine loop in breast cancer cells

et al. 2003

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We show here that nerve growth factor (NGF), the canonical neurotrophic factor, is synthesized and released by breast cancer cells. High levels of NGF transcript and protein were detected in breast cancer cells by reverse transcription-PCR, Western blotting, ELISA assay and immunohistochemistry. Conversely, NGF production could not be detected in normal breast epithelial cells at either the transcriptional or protein level. Confocal analysis indicated the presence of NGF within classical secretion vesicles. Breast cancer cell-produced NGF was biologically active, as demonstrated by its ability to induce the neuronal differentiation of embryonic neural precursor cells. Importantly, the constitutive growth of breast cancer cells was strongly inhibited by either NGF-neutralizing antibodies or K-252a, a pharmacological inhibitor of NGF receptor TrkA, indicating the existence of an NGF autocrine loop. Together, our data demonstrate the physiological relevance of NGF in breast cancer and its potential interest as a marker and therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nerve growth factor overexpression and autocrine loop in breast cancer cells

et al. 2003

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“…19 In addition, the inhibitory response to tamoxifen was expected, 3 since we previously described that MMTV-neu tumors are positive for estrogen receptors, 14 while no inhibitory effect is usually attributed to BES and DES. These features make the results achieved in our model relevant for human pathology, in particular with regard to human ER-positive breast tumors.…”

Section: Figure 2 Effect Of Different Treatments On Metastasization mentioning

confidence: 97%

Combined effects on tumor growth and metastasis by anti-estrogenic and antiangiogenic therapies in MMTV-neu mice

et al. 2002

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Breast cancer in women is a major health problem, causing a great deal of suffering and a high number of deaths. So far, early diagnosis followed by surgery is the only way to cure the disease, while therapeutic protocols for women at an advanced stage of the disease are still unsatisfactory and, in the long term, metastatic breast cancer is still associated with high treatment failure. 1 In humans, both chemotherapy and hormonal approaches for the management of the advanced disease are of great clinical relevance. Various drugs, including taxol, are active against disseminated breast cancer. 2 In addition, in patients with estrogen receptor positive tumors, antiestrogens, and tamoxifen in particular, have been widely used. 3 Many randomized trials have shown that postsurgical tamoxifen (TAM) treatment significantly reduces the growth of hormone receptor-positive breast cancer. Recently, the efficacy of TAM for chemoprevention of breast tumors has been evaluated, and the data from the Breast Cancer Prevention Trial have demonstrated that TAM administration reduces the incidence of estrogen receptor-positive, but not receptor-negative tumors. 4,5 More recently, inhibition of tumor angiogenesis was investigated as a therapeutic strategy that can inhibit Correspondence: MG Sacco, CNR-ITB, Via Fratelli Cervi, 93, 20090 Segrate (MI)

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“…Overexpression of EGFR and Her-2 have been reported to be associated with higher grades or reduced survival in a variety of cancers, including breast, colorectal, and head and neck cancers (for a review, see Klijn et al, 1992;Salomon et al, 1995). Several molecular therapeutic agents against EGFR or Her-2, such as Cetuximab and Herceptin, have been studied in clinical trials (Colomer et al, 2001;Robert et al, 2002). Although several studies have found overexpression of EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies.…”

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confidence: 99%

Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area

et al. 2003

Br J Cancer

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Although several studies have found overexpression of epidermal growth factor receptor (EGFR) proteins EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies. We examined the expression and clinical association of these molecules with oral squamous cell carcinoma in an area where betel chewing is prevalent. EGFR and Her-2 proteins were measured in 59 paired (grossly normal and cancer) tissues by an enzyme immunoassy method. The cutoff value for gene overexpression was defined as the level of mean expression in normal tissue plus two s.d. A total of 59% of the patients consumed alcohol, 90% smoked tobacco, and 90% chewed betel quid. Of the patients assayed, 34 (58%) and 24 (41%) had EGFR and Her-2 overexpression, with average 3.5-and 1.5-fold elevations. EGFR overexpression has been shown to be statistically associated with T stage, N stage, overall TMN stage, primary tumour depth, lymph node extra-capsular spread, and poor survival. Her-2 overexpression, however, did not demonstrate a similar association with clinicopathological parameters or therapeutic outcome. On multivariant analysis, EGFR overexpression (P ¼ 0.041) and N stage (P ¼ 0.024) were the only independent factors for overall survival. These results indicate that the molecular targeting therapy to EGFR may be a treatment for oral cavity cancer in the betel quid-chewing prevalent area.

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Herceptin: From the Bench to the Clinic

Cited by 41 publications

References 28 publications

Nerve growth factor overexpression and autocrine loop in breast cancer cells

Nerve growth factor overexpression and autocrine loop in breast cancer cells

Combined effects on tumor growth and metastasis by anti-estrogenic and antiangiogenic therapies in MMTV-neu mice

Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area

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