EGF Receptor Inhibition by Antibody as Anticancer Therapy

Mendelsohn, John; Baselga, J.; Wu, Xipu; Peng, Dan; Brown, Caroline; Chou, Joseph H.; Masui, Hideo; Fan, Zhen

doi:10.1007/978-3-662-03391-3_12

Cited by 47 publications

(57 citation statements)

References 24 publications

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“…Therefore, chemotherapy has been widely combined with mAbs which suppress advantageous factors for tumor cell growth or survival, e.g. anti-glycoprotein P, 37) anti-interleukin 6,38) anti-EGF receptor, 39,40) or anti-VEGF. 41) Many of them enhanced the cytotoxicity of chemotherapeutic agents in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation

Yoshida

Kawaguchi

Sato

et al. 2002

Japanese Journal of Cancer Research

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Small cell lung cancer (SCLC) cell lines specifically express ganglioside GD2, and anti-GD2 monoclonal antibodies (mAbs) caused suppression of cell growth and induced apoptosis of SCLC cells with single use. Here, enhancement of the cytotoxic effects of various anti-cancer drugs with an anti-GD2 mAb was demonstrated. The cytotoxicity of all six drugs examined was markedly enhanced, i.e. 2.4-7.8-fold increase of cell sensitivity in terms of IC 50 . In particular, the combination of cisplatin (CDDP) with an anti-GD2 mAb resulted in prominent enhancement of cytotoxicity even in low-moderate GD2-expressing lines. The anti-GD2 mAb induced weak activation of c-Jun terminal kinase (JNK) in SCLC cells, and all anti-cancer drugs also induced its activation to various degrees. When CDDP and an anti-GD2 mAb were used together, significantly stronger JNK activation was observed corresponding to the cytotoxic effects, suggesting that synergistic phosphorylation of JNK with two reagents induced prominent apoptosis. The essential role of JNK in the induction of SCLC apoptosis with CDDP and anti-GD2 mAb was confirmed by experiments with a JNK inhibitor, curcumin. These results suggest that anti-GD2 mAbs would be very efficient in combination with anti-cancer drugs, both to achieve SCLC-specific cytotoxicity and to enhance its magnitude. Key words: Apoptosis -Small cell lung cancer -Chemotherapy -JNK -GD2Gangliosides are enriched in nervous tissues of vertebrates 1) and their expression is spatio-temporally regulated.2) In human malignant tumor cells, neuroectodermderived tumor cells such as melanomas, neuroblastomas, and gliomas frequently express characteristic gangliosides for individual tumor types.3-6) Sarcomas, 7) gastric cancers, 8,9) T cell leukemias [10][11][12] and small cell lung cancer (SCLC) cells 13) also express specific gangliosides. Specific monoclonal antibodies (mAbs) to these tumor-associated ganglioside antigens have been utilized for diagnosis, 14,15) prediction of the prognosis, 16,17) and detection of residual tumors.18) In particular, anti-ganglioside mAbs have been tried for immunotherapy of melanomas 19,20) and neuroblastomas. 21)During the early stage of mAb application, anti-GD3 mAb R24 was used for the first time in the treatment of recurrent melanomas, and showed the ability to reduce the tumor size or halt the progression.19) Anti-GD2 mAb was also applied in the treatment of neuroblastomas to extend remission.22) Moreover, a human mAb reactive with GD2 was tried for cutaneous melanomas with some effects. 20)However, further development of antibody therapy has not been successful mainly due to xenogeneic immunogenicity of mouse antibodies and poor penetration of antibodies into tumor tissues.Recently, application of mAbs for the treatment of various cancers has been re-evaluated based on the progress in recombinant molecular technology and protein engineering with site-directed mutagenesis. Anti-c-erbB2/HER2/neu mAb was used in the therapy of advanced stages of breast cancers 23) and anti-CD20 mAb ...

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Section: Discussionmentioning

confidence: 99%

An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation

Yoshida

Kawaguchi

Sato

et al. 2002

Japanese Journal of Cancer Research

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“…Furthermore, occlusion of the ligand-binding site by cetuximab competitively inhibits endogenous ligand binding, thereby preventing dimerization and subsequent activation of the intrinsic receptor tyrosine kinase activity. [17][18][19][20] In combination with radiotherapy, cetuximab has demonstrated important activity in patients with locally advanced SCCHN. 21,22 In a randomized Phase III study, the addition of cetuximab to radiotherapy significantly prolonged overall survival by nearly 20 months versus radiotherapy alone (49 months vs 29.3 months; P 5 .03).…”

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confidence: 99%

Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum‐based therapies

Vermorken

Herbst

León

et al. 2008

Cancer

191

118

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A novel aryl‐bridged triphenylamine derivative, 7‐t‐butyl‐5,5,9,9‐tetraaryl‐13b‐aza‐naphtho[3,2,1‐de]anthracene (ABTPA) was designed and synthesized. The alternating copolymers of ABTPA/dihexylfluorene (P1) and triphenylamine (TPA)/dihexylfluorene (P2) were synthesized by Suzuki coupling reaction. P1 shows excellent thermal stability with a decomposition temperature of 440 °C and a glass‐transition temperature of 326 °C. The HOMO energy levels of the two polymers are very close (−5.15 eV for P1 and −5.13 eV for P2). The maximum absorption peak of P1 is red shifted by 23 nm with respect to P2, because the incorporation of ABTPA units into the PF backbone enhances the electronic conjugation degree compared with the case of TPA units. The rigidity and the steric hindrance of the ABTPA in P1 result in a small Stokes shift and almost the same emission spectra of P1 between its film and solution. A PLED with simple configurations of ITO/P1/TNS (tetranaphthalen‐2‐yl‐silane)/Alq3 (tris(8‐hydroxyquinolinolato)aluminum)/Al emits a blue light with emission peak at 436 nm, and exhibits a maximum current efficiency of 1.89 cd/A and a maximum luminance of 4183 cd/m2, which is superior to the device with P2 as emissive layer under the identical conditions. These results indicate that ABTPA unit could be a very promising candidate to replace TPA unit and find widely application in organic/polymeric optoelectronic materials. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3651–3661, 2009

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“…Transforming growth factor a and erbb-1 are upregulated in malignancies of many different organs, including HCC. Novel therapeutic approaches have been focusing on the possible benefit of blocking TGFa-evoked signal transduction on the cell surface, for example, by erbb-1 blockade (Levitzki and Gazit, 1995;Mendelsohn, 1997). The present study shows that treatment with mature TGFa stimulated DNA synthesis rather in proTGFa-neg than in proTGFa-pos hepatocytes, which was abrogated by an erbb-1-specific tyrosine kinase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

“…The ectodomain of the pro-peptide may be shed from the cell surface, where it may bind to and activate the erbb-1 receptor, that confers the growth signal via phosphorylation cascades to the nucleus (Massagué, 1990;Yarden and Sliwkowski, 2001). Considering the upregulation of TGFa in human malignancies, including liver cancer, hope focuses on the possible therapeutic benefit of blocking TGFaevoked signal transduction on the cell surface, for example, by blockade of the receptor or of ligand -receptor interactions (Levitzki and Gazit, 1995;Mendelsohn, 1997). In a recent study, however, we have shown that hepatocytes in the intact liver and in primary culture synthesise proTGFa that translocates to the nucleus, where it appears to be involved in the mitogenic response of the cell (Grasl-Kraupp et al, 2002).…”

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confidence: 99%

Inherent growth advantage of (pre)malignant hepatocytes associated with nuclear translocation of pro-transforming growth factor α

et al. 2004

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The pro-peptide of transforming growth factor a (proTGFa) was recently found in hepatocyte nuclei preparing for DNA replication, which suggests a role of nuclear proTGFa for mitogenic signalling. This study investigates whether the nuclear occurrence of the propeptide is involved in the altered growth regulation of (pre)malignant hepatocytes. In human hepatocarcinogenesis, the incidence of proTGFa-positive and replicating nuclei gradually increased from normal liver, to dysplastic nodules, to hepatocellular carcinoma. ProTGFa-positive nuclei almost always were in DNA synthesis. Also, in rat hepatocarcinogenesis, proTGFa-positive nuclei occurred in (pre)malignant hepatocytes at significantly higher incidences than in unaltered hepatocytes. For functional studies unaltered (GSTp À ) and premalignant (GSTp þ ) rat hepatocytes were isolated by collagenase perfusion and cultivated. Again, DNA synthesis occurred almost exclusively in proTGFa-positive nuclei. GSTp þ hepatocytes showed an B3-fold higher frequency of proTGFa-positive nuclei and DNA replication than GSTp À cells. Treatment of cultures with the mitogen cyproterone acetate (CPA) elevated the incidence of proTGFa-positive nuclei and DNA synthesis in parallel. Conversely, transforming growth factor b1 (TGFb1) lowered both. These effects of CPA and TGFb1 were significantly more pronounced in GSTp þ than in GSTp À hepatocytes. In conclusion, nuclear translocation of proTGFa increases in the course of hepatocarcinogenesis and appears to be involved in the inherent growth advantage of (pre)malignant hepatocytes.

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EGF Receptor Inhibition by Antibody as Anticancer Therapy

Cited by 47 publications

References 24 publications

An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation

An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation

Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum‐based therapies

Inherent growth advantage of (pre)malignant hepatocytes associated with nuclear translocation of pro-transforming growth factor α

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