Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Randomized Controlled Trial
Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer--a study of CALGB 9581 and 89803.
Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors. ⋯ We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.
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Trastuzumab resistance has been linked to activation of the phosphoinositol 3-kinase (PI3K) pathway. Phosphatase and tensin homolog (PTEN) is a dual phosphatase that counteracts the PI3K function; PTEN loss leads to activation of the Akt cascade and the downstream mammalian target of rapamycin (mTOR). Preclinical studies demonstrated that mTOR inhibition sensitized the response to trastuzumab in mice with HER2 overexpressing and PTEN-deficient breast xenografts. Our trial evaluated the safety and efficacy of the combination of everolimus and trastuzumab in women with HER2-overexpressing metastatic breast cancer (MBC) that progressed on trastuzumab-based therapy. ⋯ Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumab-resistant HER2-overexpressing MBC.
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Many phase III trials presented at annual meetings of the American Society of Clinical Oncology (ASCO) remain unpublished. The results of these unpublished trials, if more generally known, might have an impact on clinical practice. ⋯ A substantial number of cancer clinical trials with potential influence on clinical practice remain unpublished and many other trials are published after a substantial delay. Nonpublication of clinical trials breaks an implicit contract with participants, institutional review boards, and sponsors.