May 1 Clinical Cancer Research Highlights

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Selected Articles from the May 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the May 1 issue of Clinical Cancer Research.

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Oncoproteins An Effective HPV Biomarker

Castle et al.
Page 2599

Carcinogenic human papillomavirus (HPV) mRNA for E6 and E7 oncoproteins may be a more specific biomarker for cervical precancer and cancer than carcinogenic HPV DNA, but few studies have evaluated carcinogenic HPV E6/E7 mRNA detection using clinical specimens. Castle et al. evaluated a prototype assay that collectively detects oncogenes E6/E7 mRNA for 14 carcinogenic HPV genotypes on a sample of liquid cytology specimens masked to clinical data and to the presence of HPV genotypes detected by PGMY09/11 L1 consensus primer PCR assay. The authors found that carcinogenic HPV E6/E7 mRNA is a potentially useful biomarker for detection of cervical precancer and cancer and therefore warrants further evaluation.

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Vitamin Supplementation Enhances Maximally Tolerated Doses of Pemetrexed

Takimoto et al.
Page 2675

Pemetrexed is a novel antifolate antimetabolite approved for use in advanced non-small cell lung cancer patients and in combination chemotherapy for patients with malignant mesothelioma. Takimoto et al. found that folic acid vitamin supplementation resulted in significantly higher maximally tolerated doses (>500 mg/m²) of pemetrexed, and this supplemented regimen was active in patients with mesothelioma and other solid tumors. Coadministration of folic acid did not alter qualitatively the types of dose-limiting toxicities observed, with neutropenia and thrombocytopenia being the most common. Further exploration of the promising therapeutic potential of pemetrexed at doses >500 mg/m² administered with vitamin supplementation is warranted.

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Insulin Controls Cancer Cachexia    

Lundholm et al.
Page 2699

Weight loss is detrimental to the recovery of cancer patients. Lundholm et al. evaluated whether daily insulin treatment for weight-losing cancer patients attenuates progression of cancer cachexia and improves metabolism and physical functioning in palliative care. Patient characteristics at randomizations were almost identical in study and control groups. Insulin treatment for 193 ± 139 days (mean ± SD) significantly stimulated carbohydrate intake, decreased serum-free fatty acids, and increased whole body fat, particularly in trunk and leg compartments, although fat-free lean tissue mass was unaffected. The authors concluded that insulin is a significant metabolic treatment in multimodal palliation of weight-losing cancer patients.

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Focused Ultrasound Triggers Heat-Sensitive Liposomes

Dromi et al.
Page 2722

The authors set out to determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin (DOX) in tumors. Local energy was deposited noninvasively using an imaged-guided, high intensity focused ultrasound (HIFU) system in combination with a tailored formulation of liposomal chemotherapy to enhance drug delivery and tumor growth inhibition in mice. Dromi et al. found that this novel drug-device combination showed augmentation of therapeutic response by combining heat-deployed liposomal doxorubicin with HIFU exposures in pulsed mode. These noncontinuous exposures limited heat generation, rendering them nondestructive. Such a tailored energy/engineered drug combination could become a more common paradigm in the arsenal against cancer.

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