In BMC Cancer this week, researchers in Canada report a combination treatment that inhibits the growth of HER2-expressing breast cancer cells and tumors, regardless of the patient's sensitivity to trastuzumab. The team combined the EGFR inhibitor gefitinib and the mTOR inhibitor RAD001, and applied them to trastuzumab sensitive and trastuzumab resistance breast cancer cell lines. The combination treatment inhibited cell growth in vitro irrespective of trastuzumab sensitivity, the team says. In addition, the drugs worked very well together, the authors observed, writing, "the most striking and consistent therapeutic effect of the combination was increased inhibition of the mTOR pathway (in vitro and in vivo) and EGFR signaling in vivo relative to the single drugs."
Also in BMC Cancer this week, researchers in China assess the clinical significance and prognostic impact of an extramural metastasis in colorectal cancer. The team analyzed data from 1,215 patients with colorectal cancer who underwent surgical resection between 2000 and 2005. Metastases outside was detected in 167 of these patients, and was significantly higher in patients with large tumors, deeper invasive depth, and more lymph node metastasis. "After curative operation, overall survival was significantly worse for patients with extramural metastasis than those without," the authors write. "Multivariate analysis identified extramural metastasis as an independent prognostic factor."
Finally in BMC Cancer this week, researchers in Sweden and the UK write that isoforms of the CD44 cell adhesion molecule can correlate with tumor subtypes and cancer stem cell markers in breast cancer. CD44 is aberrantly expressed in many breast tumors and has been implicated in the metastatic process. For this study, the team analyzed the expression of four CD44 isoforms, and total CD44 expression in 187 breast tumors and 13 cell lines. The team found that breast cancer cells showed a heterogeneous expression pattern of the CD44 isoforms, with different tumor subtypes being associated with elevated expression of specific isoforms. "We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER, and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways," the authors write. "Efforts to link CD44 to cancer stem cells and tumor progression should consider the expression of various CD44 isoforms."