March 1 2008 Clinical Cancer Research Highlights

Targeted Intraoperative Radiotherapy (TARGIT) enables delivery of radiotherapy to the tumor bed immediately after surgical excision and is currently used in clinical trials for the treatment of localized breast cancer. Belletti and colleagues report that TARGIT alters the molecular composition and biological activity of surgical wound fluids. They found that wound fluids harvested from TARGIT-treated breast cancer patients were much less effective than fluids from untreated patients at stimulating proliferation and migration of breast cancer cells. This work provides a molecular explanation for the harmful effects of surgery in the control of breast cancer relapse and supports the concept that local perioperative treatments may represent an effective strategy.  

 

Basal-like breast cancer is an aggressive subtype best recognized through gene expression profiling. Clinically, a standard approach based on an ER, PR and HER2 triple negative phenotype is thought to identify the disease, but many pathologists advocate including additional positive immunomarkers (such as EGFR and CK 5/6) to aid in identification. Using tissue microarrays to study over 4,000 cases of breast cancer, Cheang and colleagues compared the prognostic significance of the standard triple negative approach to a five panel approach (ER, PR, HER2, EGFR, and CK5/6). They found that the poor prognosis of triple negative cancers is conferred almost entirely by the subset positive for basal markers, supporting use of a five marker surrogate immunopanel to clinically define basal breast cancer. 

Cancer stem cells are rare populations of cells with enhanced self-renewal capabilities and molecular features that confer resistance to conventional chemotherapy. Compared with normal hematopoietic stem cells, leukemia stem cells have elevated levels of nuclear NF-κB and show increased sensitivity to proteasome inhibition. Attar and colleagues studied the safety and tolerability of bortezomib, a proteasome inhibitor capable of inhibiting NF-κB, in patients with acute myeloid leukemia (AML). They defined the pharmacokinetics of bortezomib and determined that bone marrow expression of CD74 was associated with complete remission. This work provides a framework for studying bortezomib in combination with chemotherapy in patients with AML.