October 2007 MCT Highlights

Selected Articles from the October 1, 2007 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Molecular Cancer Therapeutics is published. Click on the article title to view the complete article.

View the Table of Contents for the October 2007 issue of Molecular Cancer Therapeutics

ERβ Can Be Restored in Prostate Cancer

Stettner et al.

Page 2626

The estrogen receptor-b (ERβ) controls tumor cell proliferation and loss of ER-β expression is associated with the progression of prostate cancer. Thus, ER-β is considered as a tumor suppressor in this disease. However, Stettner and colleagues found that ERβ expression lost in prostate cancer can be restored by treatments with the histone deacetylase inhibitor valproic acid and the phyto-estrogen tectorigenin. Concomitantly, tumor cell proliferation as well as the expression of genes relevant in proliferation, survival and invasion decreased. siRNA mediated knock-down of ERβ provoked the contrary and beneficial effects from phyto-estrogens were abrogated. The authors concluded that ERβ may become a therapeutic target for prostate cancer intervention.

Cetuximab Inhibits EGFR Mutants

Doody et al.

Page 2642

Mutations in the kinase domain of EGFR were recently identified among NSCLC patients, and have been established as an indicator of better response to TKIs. Doody and coauthors reported that cetuximab, an EGFR antibody, inhibits the activity of several EGFR mutants in both cell-based and in vivo models. Interestingly, cetuximab also enhances the degradation of those tested EGFR mutants when compared to wild type receptor, by a novel yet unidentified mechanism. These findings provide a better understanding on the role of EGFR in tumor development and present cetuximab as a promising regimen for NSCLC patients harboring these mutations.

Ligand Expression Mediates EGFR Antagonism

Wu et al.

Page 2652

Epidermal growth factor receptor (EGFR) has been extensively targeted in the treatment of non-small cell lung cancer, producing responses in a small number of patients. To study the role of ligand expression in mediating response to EGFR antagonism, Wu and colleagues injected NCI-H441 (EGFR and EGF/TGF-α positive) or PC14-PE6 (EGFR positive and EGF/TGF-α negative) human lung adenocarcinoma cells into the lungs of nude mice. Treatment of mice bearing NCI-H441 but not PC14-PE6 lung tumors resulted in a significant reduction in primary tumor growth, pleural effusion, and lymph node metastasis. These results strongly suggest that the response of human lung cancers growing orthotopically in mice to the inhibition of EGFR signaling is determined by ligand (EGF/TGF-α) expression by tumor cells, providing an additional explanation for the susceptibility of lung cancers to treatment with EGFR tyrosine kinase inhibitors.

DIM Sensitizes Breast Cancer Cells to Chemotherapy

Rahman et al.

Page 2757

Previous studies using 3, 3’-diindolylmethane (DIM), a stable condensation product of indole-3-carbinol (I3C) with greater bioavailability, showed superiority compared to I3C, suggesting that DIM could be an useful anti-tumor agent. Rahman and colleagues showed that DIM in combination with low-dose of Taxotere enhances the inhibition of cell growth and induction of apoptosis in breast cancer cells through inhibition of the NF-kB signaling pathway. Their findings provide experimental evidence in support of chemo-sensitizing effect of DIM against breast cancer, which could become a novel breakthrough for devising optimal therapies for breast cancer.

Tamoxifen and Persin Show Synergistic Cytotoxicity

Roberts et al.

Page 2777
While endocrine therapies such as the antiestrogen tamoxifen have had a significant impact on improving survival rates for breast cancer patients, their use is restricted to ER-positive tumors and, even within this group, intrinsic or acquired therapeutic resistance remains a major obstacle to an effective cure. Roberts and colleagues found that combining tamoxifen with a novel plant toxin, persin, resulted in a synergistic, cytotoxic effect in both ER-positive and ER-negative breast cancer cell lines, while normal breast epithelial cells were unaffected. Thus, combining endocrine and non-endocrine therapies may provide a novel strategy to enhance and broaden therapeutic efficacy, particularly against refractory disease.

October 2007 MCT Highlights

Selected Articles from the October 1, 2007 Issue

ERβ Can Be Restored in Prostate Cancer

Cetuximab Inhibits EGFR Mutants

Ligand Expression Mediates EGFR Antagonism

DIM Sensitizes Breast Cancer Cells to Chemotherapy

Tamoxifen and Persin Show Synergistic Cytotoxicity

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