Key Signaling Pathways in the Muscle-Invasive Bladder Carcinoma: Clinical Markers for Disease Modeling and Optimized Treatment

In this review we evaluate key molecular pathways and markers of MIBC. Overexpression and activation of EGFR, p63 and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy.

Alterations in PPARγ, ERBB2/3, FGFR3 gene products and their signaling along with deregulated p53, cytokeratins KRT5/6/14 in combination with the cellular proliferation (Ki-67) and cell cycle markers (p16) indicate the need for more radical treatment protocols. Similarly, the 'bell-shape' dynamics of Shh expression levels may suggest aggressive MIBC. A panel of diverse biological markers may be suitable for simulation studies of MIBC and development of an optimized treatment protocol.

METHODS - We conducted a critical evaluation of PubMed/Medline and SciFinder databases related to muscle-invasive bladder cancer (MIBC) covering the period 2009-2015. The free-text search was extended by adding the following keywords and phrases: bladder cancer, metastatic, muscle-invasive, basal, luminal, epithelial-to-mesenchymal transition, cancer stem cell, mutations, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, epigenetics, transmembrane, transcription factor, kinase, predictor, prognosis. The resulting selection of ca. 500 abstracts was further analyzed in order to select the latest publications relevant to MIBC molecular markers of immediate clinical significance. This article is protected by copyright. All rights reserved.

International journal of cancer. Journal international du cancer. 2015 Nov 06 [Epub ahead of print]

Alex Kiselyov, Svetlana Bunimovich-Mendrazitsky, Vladimir Startsev

NBIC, Moscow Institute of Physics and Technology (MIPT), 9 Institutsky Per. , Dolgoprudny, Moscow Region, 141700, Russia. , Department of Computer Science and Mathematics, Ariel University, Ariel, 40700, Israel. , Department of Oncology, State Pediatric Medical University, St. -Petersburg, 194100, Russia.



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