© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 24, 1829,
December 19, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Trastuzumab (Herceptin), a monoclonal antibody against the HER2/neu receptor, inhibits the growth of ErbB2-overexpressing breast cancer cells. Many patients with such breast cancers treated with trastuzumab will eventually develop resistance to the drug. Lu et al. (p. 1852) investigated the association of trastuzumab resistance and signaling via the insulin-like growth factor-I receptor (IGF-IR) by use of various human breast cancer cell lines. They found that trastuzumab inhibited growth of breast cancer cells overexpressing HER2/neu receptors only when IGF-IR signaling was minimized. They conclude that treatments that decrease IGF-IR signaling may prevent or delay resistance to trastuzumab.
In an accompanying editorial, Albanell and Baselga (p. 1830) note that the report by Lu et al. represents a further step toward unraveling trastuzumab resistance by showing an association between IGF-IR signaling and the trastuzumab response. If this association were also established by clinical studies, the editorialists believe that therapies should be developed targeting both IGF-IR and HER2/neu in patients with breast cancer.
Sonic Hedgehog Gene and Hair Growth After Chemotherapy
The Sonic hedgehog (Shh) gene is involved in the initiation of normal hair growth. Its expression in mouse skin when mediated by adenovirus vector accelerates initiation of the growth phase of hair follicle development. Because hair regrowth after chemotherapy-induced alopecia (hair loss) is similar to that observed in normal hair growth, Sato et al. (p. 1858) examined whether adenovirus-mediated Shh expression would accelerate hair regrowth in the skin of mice given chemotherapy. The areas of skin inoculated with adenovirus vector carrying the Shh gene showed normal hair follicles when compared with untreated naive skin or skin treated with control vector. The investigators suggest that localized, transient, enhanced expression of Shh gene in skin, mediated by an adenovirus vector, might be a future strategy to accelerate hair follicle regrowth following chemotherapy-induced alopecia.
HPV16-E7 Oncoprotein and Cervical Endothelial Cells
Human papillomavirus type 16 (HPV16) is strongly implicated in the etiology of cervical cancer. The expression of HPV16 early nuclear protein E7 in the infected epithelial cells contributes to their malignant transformation. D’Anna et al. (p. 1843) investigated the effects of extracellular E7 on cytokine production and on the cytoskeleton structure of cervical microvascular endothelial (CrMVEn) cells and vascular endothelial cells from different organs. CrMVEn cells were capable of taking up extracellular E7, which was then found to be localized to the cytoplasm. CrMVEn cells showed marked alterations in the cytoskeleton as a result of actin fiber polymerization. After treatment with E7, CrMVEn cells produced interleukin 6 and interleukin 8 at higher levels than those produced by other endothelial cells. The authors suggest that extracellular E7 can play a role in the progression and dissemination of cervical cancer via its selective effects on organ-specific endothelial cells.
Characteristics of Patients and Initial Prostate Cancer Therapy
Virtually no information is available from randomized clinical trials that compare aggressive therapies with more conservative therapies for clinically localized prostate cancer. Harlan et al. (p. 1864) examined the association of sociodemographic and clinical characteristics with four management options for prostate cancer: radical prostatectomy, radiation therapy, hormonal therapy, and watchful waiting. They observed that certain nonclinical factors were associated with specific treatments. They concluded that, in the absence of definitive information about treatment effectiveness, men with prostate cancer should be better informed about the risks and benefits of all treatment options.
Tomato Sauce Intervention for Prostate Cancer Patients
The risk of prostate cancer is lower in men reporting higher consumption of tomato products, which contain high levels of the antioxidant lycopene. Chen et al. (p. 1872) examined the effects of consumption of tomato sauce-based pasta meals on lycopene uptake and oxidative DNA damage in prostate tissue from men already diagnosed with prostate cancer. The authors found that patient compliance with the whole-food, 3-week intervention was high and resulted in statistically significantly increased concentrations of lycopene in serum and prostate tissue. Furthermore, oxidative damage in prostate tissue was statistically significantly lower in patients who participated in the intervention than in those who did not. The authors also found that serum prostate-specific antigen levels decreased after patients ate the pasta meals. The authors conclude that a constituent of tomato sauce, possibly lycopene, may have a role in the treatment of prostate cancer.
Hypoxia-Induced Drug Resistance and Nitric Oxide
The presence of hypoxic (low-O2) regions in tumors is associated with malignant progression, metastasis, and resistance to drug and radiation therapy. The mechanism for hypoxia-induced drug resistance is unknown, but oxygen is required for the production of nitric oxide (NO) and NO may block components of the adaptation to hypoxia. In this issue, Matthews et al. (p. 1879) show that hypoxia appears to increase drug resistance in tumor cells by inhibiting NO production. Tumor cells exposed to low levels of oxygen rapidly developed resistance to two different chemotherapy drugs, as did tumor cells exposed to high oxygen levels plus an inhibitor of NO production. Conversely, treating cells with NO mimetics at the onset of exposure to hypoxia attenuated the development of drug resistance. The authors note that their results, in addition to providing insights into the mechanism of hypoxia-induced drug resistance, raise the possibility of a potential therapeutic role for NO mimetics.
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