Abstract
Angiotensin inhibitors are standard drugs in cardiovascular and renal diseases that have antihypertensive and antifibrotic properties. These drugs also exert their antifibrotic effects in cancer by reducing collagen and hyaluronan deposition in the tumor stroma, thus enhancing drug delivery. Angiotensin II signaling interferes with the secretion of the cytokine TGF-β-a known driver of malignancy. TGF-β stimulates matrix production in cancer-associated fibroblasts, and thus drives desmoplasia. The effect of TGF-β on cancer cells itself is stage-dependent and changes during malignant progression from inhibitory to stimulatory. The intracellular signaling for the TGF-β family can be divided into an SMAD-dependent canonical pathway and an SMAD-independent noncanonical pathway. These capabilities have made TGF-β an interesting target for numerous drug developments. TGF-β is also an inducer of epithelial-mesenchymal transition (EMT). EMT is a highly complex spatiotemporal-limited process controlled by a plethora of factors. EMT is a hallmark of metastatic cancer, and with its reversal, an important step in the metastatic cascade is characterized by a loss of epithelial characteristics and/or the gain of mesenchymal traits.
Highlights
epithelial–mesenchymal transition (EMT) underlies an extensive influence of environmental factors upon the cancer cells, necessitating control and crosstalk between different cells orchestrated by EMT-activating-transcription factors (EMT-TFs)
SNAI1 or TWIST1 were knocked out in pancreatic cancer depending on cell background, yielding an individual reaction set for every tumor type and EMT‐
Angiotensin inhibitors are such candidate drugs—especially those acting on AT-1 signaling, which has been found to be an important pro-fibrotic signaling
Summary
Despite that well-defined molecular targets have been identified, personalized cancer therapies have not been found for all cancer types. Excellent results for one type of therapy were shown in the treatment of Philadelphia chromosome-positive (t(9;22)(q34;q11.2)) chronic myelogenous leukemia (CML) with imatinib as a designed drug that attacks the BCR–ABL fusion product [2,3]. In contrast to “liquid” cancers, “solid” cancers generate obstacles for drug delivery. It is still un clear which effects are responsible for poor drug penetration into solid tumors [4]. As tumors are very heterogeneous, these factors likely do not all apply to the same extent for all cancer types. The crosslink to transforming growth factor-β (TGF-β) signaling and its impacts on cancer therapy are covered. TGF-β is a potent inducer of the highly complex epithelial–mesenchymal-transition (EMT), which are covered
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
