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Over the last decade, the use of targeted therapies has immensely increased in the treatment of cancer. However, treatment for endometrial carcinomas (ECs) has lagged behind, although potential molecular markers have been identified. This is particularly problematic for the type II ECs, since these aggressive tumors are usually not responsive toward the current standard therapies. Therefore, type II ECs are responsible for most EC-related deaths, indicating the need for new treatment options. Interestingly, molecular analyses of type II ECs have uncovered frequent genetic alterations (up to 40%) in PPP2R1A, encoding the Aα subunit of the tumor suppressive heterotrimeric protein phosphatase type 2A (PP2A). PPP2R1A mutations were also reported in type I ECs and other common gynecologic cancers, albeit at much lower frequencies (0-7%). Nevertheless, PP2A inactivation in the latter cancer types is common via other mechanisms, in particular by increased expression of Cancerous Inhibitor of PP2A (CIP2A) and PP2A Methylesterase-1 (PME-1) proteins. In this review, we discuss the therapeutic potential of direct and indirect PP2A targeting compounds, possibly in combination with other anti-cancer drugs, in EC. Furthermore, we investigate the potential of the PP2A status as a predictive and/or prognostic marker for type I and II ECs.
Pubmed ID: 31214504
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Public database with millions of high-resolution images showing the spatial distribution of proteins in different normal human tissues and cancer types, as well as different human cell lines. The data is released together with application-specific validation performed for each antibody, including immunohistochemisty, Western blot analysis and, for a large fraction, a protein array assay and immunofluorescent based confocal microscopy. The database has been developed in a gene-centric manner with the inclusion of all human genes predicted from genome efforts. Search functionalities allow for complex queries regarding protein expression profiles, protein classes and chromosome location. Antibodies included have been analyzed using a standardized protocol in a single attempt without further efforts to optimize the procedure and therefore it cannot be excluded that certain observed binding properties are due to technical rather than biological reasons and that further optimization could result in a different outcome. Submission of antibodies: The Swedish Human Proteome Atlas (HPA) program, invites submission of antibodies from both academic and commercial sources to be included in the human protein atlas. All antibodies will be validated by the HPA-program by a standard procedure and antibodies that are accepted will be use in the tissue- profiling program to generate high-resolution immunohistochemistry images representing a wide spectrum of normal tissues and cancer types.
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