We suggest that targeting fibroblast-to-myofibroblast transition with halofuginone significantly slow tumor progression and when combined with low doses of chemotherapy a major anti-tumoral effect is achieved, avoiding the need of high dose of chemotherapy MEK162 cell line without impairing treatment efficacy. O184 Stromal Caveolin-1 Predicts Recurrence and Clinical Outcome in DCIS and Human Breast Cancers Agnes K. Witkiewicz1, Abhijit Dasgupta1, Isabelle
Mercier1, Gordon Schwartz3, Celina Kleer2, Richard G. Pestell1, Federica Sotgia1, Michael P. Lisanti 1 1 Cancer Biology; Medical Oncology; and Pathology, Kimmel Cancer Center; Thomas Jefferson University, Philadelphia, PA, USA, 2 Pathology, University of Michigan, Ann Arbor, MI, USA, 3 Surgery, Thomas Jefferson University, Philadelphia,
PA, USA Previously, we showed that caveolin-1 (Cav-1) expression is down-regulated in human breast cancer-associated fibroblasts. Here, we discuss recent evidence that an absence of stromal Cav-1 expression in human breast cancers is a powerful single independent predictor of early disease recurrence, metastasis and poor clinical outcome. These findings have now been validated in two independent patient populations. Importantly, the VS-4718 supplier predictive value of stromal Cav-1 is independent of epithelial marker status, making stromal Cav-1 a new “universal” or “widely-applicable” breast cancer prognostic marker. We propose based on the CP673451 chemical structure expression of stromal Cav-1, that breast cancer patients could
be stratified into high-risk and low-risk groups. High-risk patients showing an absence of stromal Cav-1 should be offered more aggressive therapies, such as anti-angiogenic approaches, in addition to the standard therapy regimens. Mechanistically, loss of stromal Cav-1 is a surrogate biomarker for increased cell cycle progression, growth factor secretion, “stemness”, and angiogenic potential in the tumor microenvironment. Since almost all cancers develop within the context of a stromal Loperamide microenvironment, this new stromal classification system may be broadly applicable to other epithelial and non-epithelial cancer subtypes, as well as “pre-malignant” lesions (carcinoma in situ). We conclude that Cav-1 functions as a tumor suppressor in the stromal microenvironment. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, Kleer CG, Brody JR, Lisanti MP.Am J Pathol. 2009 Jun;174(6):2023–34. O185 Antimetastasic Action of Parp Inhibition in Melanoma trough Counteracting Angiogenesis and emt Transition F.