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Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment.

Publication ,  Journal Article
Augustine, CK; Yoshimoto, Y; Gupta, M; Zipfel, PA; Selim, MA; Febbo, P; Pendergast, AM; Peters, WP; Tyler, DS
Published in: Cancer Res
May 15, 2008

Malignant transformation in melanoma is characterized by a phenotype "switch" from E- to N-cadherin, which is associated with increased motility and invasiveness of the tumor and altered signaling, leading to decreased apoptosis. We hypothesized that the novel pentapeptide (ADH-1), which disrupts N-cadherin adhesion, could sensitize melanoma tumors to the cytotoxic effects of chemotherapy. N-cadherin-expressing human melanoma-derived cell lines were used to generate xenografts in animal models to study isolated limb infusion with melphalan and systemic chemotherapy with temozolomide. We report here that melphalan in combination with ADH-1 significantly reduced tumor growth up to 30-fold over melphalan alone. ADH-1 enhancement of response to melphalan was associated with increased formation of DNA adducts, increased apoptosis, and intracellular signaling changes associated with focal adhesions and fibroblast growth factor receptors. Targeted therapy using an N-cadherin antagonist can dramatically augment the antitumor effects of chemotherapy and is a novel approach to optimizing treatment for melanoma.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

May 15, 2008

Volume

68

Issue

10

Start / End Page

3777 / 3784

Location

United States

Related Subject Headings

  • Temozolomide
  • Rats, Nude
  • Rats
  • Phenotype
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Models, Biological
  • Melphalan
  • Melanoma
  • Immunotherapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Augustine, C. K., Yoshimoto, Y., Gupta, M., Zipfel, P. A., Selim, M. A., Febbo, P., … Tyler, D. S. (2008). Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment. Cancer Res, 68(10), 3777–3784. https://doi.org/10.1158/0008-5472.CAN-07-5949
Augustine, Christina K., Yasunori Yoshimoto, Mukur Gupta, Patricia A. Zipfel, M Angelica Selim, Phillip Febbo, Ann Marie Pendergast, William P. Peters, and Douglas S. Tyler. “Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment.Cancer Res 68, no. 10 (May 15, 2008): 3777–84. https://doi.org/10.1158/0008-5472.CAN-07-5949.
Augustine CK, Yoshimoto Y, Gupta M, Zipfel PA, Selim MA, Febbo P, et al. Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment. Cancer Res. 2008 May 15;68(10):3777–84.
Augustine, Christina K., et al. “Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment.Cancer Res, vol. 68, no. 10, May 2008, pp. 3777–84. Pubmed, doi:10.1158/0008-5472.CAN-07-5949.
Augustine CK, Yoshimoto Y, Gupta M, Zipfel PA, Selim MA, Febbo P, Pendergast AM, Peters WP, Tyler DS. Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment. Cancer Res. 2008 May 15;68(10):3777–3784.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

May 15, 2008

Volume

68

Issue

10

Start / End Page

3777 / 3784

Location

United States

Related Subject Headings

  • Temozolomide
  • Rats, Nude
  • Rats
  • Phenotype
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Models, Biological
  • Melphalan
  • Melanoma
  • Immunotherapy