Regulation of tumorigenic Wnt signaling by cyclooxygenase-2, 5-lipoxygenase and their pharmacological inhibitors: A basis for novel drugs targeting cancer cells?

摘要: Canonical Wnt signaling is a highly conserved pathway with prominent role in embryogenic development, adult tissue homeostasis, cell polarization, stem biology, differentiation, and proliferation. Furthermore, canonical of pivotal importance the pathogenesis number cancer types crucially affects tumor initiation, proliferation, apoptosis, metastasis. Reports over last decade have provided strong evidence for pathophysiological non-malignant classical inflammatory neurodegenerative diseases. Although, several agents suppressing at different levels been identified, development clinically relevant Wnt-inhibiting remains challenging due to selectivity toxicity issues. Several studies shown that long-term administration non-steroidal anti-inflammatory drugs protects against colon potentially other by interfering both COX pathway. Our own suppress targeting pro-inflammatory enzyme 5-lipoxygenase which key pathophysiologically involved synthesis leukotrienes. we found direct link between pathways, essential maintenance leukemic cells. Accordingly, genetic pharmacological inhibition led an impairment Wnt-dependent acute chronic myeloid We believe inhibitors might represent novel type inhibitor activating naturally occurring mechanism suppression non-toxic, least mice, well tolerated patients.