Fatime Szalai, Ildikó Krencz, Dorottya Moldvai, Gábor Petővári, Titanilla Dankó, Noémi Nagy, Gergő Papp, Judit Pápay, Anna Sebestyén, Dániel Sztankovics
{"title":"[he importance of mTOR hyperactivity and RICTOR amplification, and the associated targeted therapy possibilities in malignant tumours].","authors":"Fatime Szalai, Ildikó Krencz, Dorottya Moldvai, Gábor Petővári, Titanilla Dankó, Noémi Nagy, Gergő Papp, Judit Pápay, Anna Sebestyén, Dániel Sztankovics","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Failures of anti-tumour therapies and drug resistance initiate difficulties in cancer treatments often caused by alterations in signalling network activity, including PI3K/Akt/mTOR hyperactivity due to oncogenic mutations. In this review, we summarise the relevance of mTOR (mechanistic target of rapamycin) dysregulation identified decades ago, which is now known to be characteristic of many tumours. In this context, we present differences in activity, function and testability of mTOR kinase complexes (mTORC1 and mTORC2) differing in structure, regulatory mechanisms and inhibitor sensitivity. We highlight that genetic alterations, including RICTOR amplification and associated mTOR hyperactivity, are relevant in targeted therapy development. It is recommended to investigate mTOR profile activity in patients for whom mTOR inhibitor therapies are considered since the current first-generation mTOR inhibitors (rapamycin and analogues) may be ineffective in case of mTORC2 hyperactivity. Ongoing phase trials of new inhibitors and combination therapies are promising in advanced stage patients selected by molecular markers.</p>","PeriodicalId":94127,"journal":{"name":"Magyar onkologia","volume":"67 3","pages":"165-180"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gergely Huszty, László Bihari, László Gráf, Attila Szijártó, Szabolcs Máté
{"title":"[Surgery of peritoneal surface malignancies - surgical cytoreduction and hyperthermic intraperitoneal chemotherapy].","authors":"Gergely Huszty, László Bihari, László Gráf, Attila Szijártó, Szabolcs Máté","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Peritoneal carcinosis has historically been considered as inoperable, although the technique of its resesection together with high dose intraperitoneal chemotherapy potentiated by heat has been described decades ago. It has not became a widely practiced routine except in specialized centers - the complex technique, weakly standardized but resource demanding chemotherapy, lacking financial background and the many times questionable clinical benefit at a cost of high surgical load might have been the key factors. Refined technology, developing chemotherapy protocols together with growing clinical evidence are now more sharply delineating the range of indications where the procedure might be beneficial, increases survival, or is the only curative therapy. These include tumors of the appendix and pseudomyxoma peritonei, mesothelioma, and selected cases of ovarian, colorectal and gastric cancer. In addition to technical description of the intervention, we summarize the currently valid indications and describe our institutional protocol for the treatment of appendiceal malignancies.</p>","PeriodicalId":94127,"journal":{"name":"Magyar onkologia","volume":"67 3","pages":"247-258"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Vízkeleti, Andrea Ladányi, Orsolya Papp, Viktória Doma, Sarolta Kárpáti, Erzsébet Rásó, Tamás Barbai, József Tímár
{"title":"[Potential role of type I interferon in the genetic progression of melanoma].","authors":"Laura Vízkeleti, Andrea Ladányi, Orsolya Papp, Viktória Doma, Sarolta Kárpáti, Erzsébet Rásó, Tamás Barbai, József Tímár","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have followed the genomic progression of cutaneous melanoma in visceral metastases using genome-wide copy number analysis. We have detected an increased chromosomal instability due to the loss of several DNA repair genes. Furthermore, we found co-amplifications of HGF and MET genes in metastases. The most interesting finding was gene amplifications of several, mostly IFN-regulated immune cell genes in lung metastases. Next we have defined a type I IFN resistance gene expression signature (GES) using human cell lines, several elements of which were proved to be stable in vitro and in vivo as well. The components of this GES have been detected in TCGA as well as in publicly available datasets of immunotherapy-treated melanoma cases. In case of samples from previously IFN-treated melanoma cases we have identified treatment-specific genomic alterations (predominantly amplifications) which were most characteristic for brain metastases.</p>","PeriodicalId":94127,"journal":{"name":"Magyar onkologia","volume":"67 3","pages":"215-221"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcell Baranyi, Balázs Hegedűs, Eszter Molnár, József Tóvári, Ivan Ranđelović, András Perczel, László Buday, György Keserű, József Tímár
{"title":"[Farnesyltransferase inhibitors have antitumoral effects in mutant KRAS containing cancer cells in preclinical models].","authors":"Marcell Baranyi, Balázs Hegedűs, Eszter Molnár, József Tóvári, Ivan Ranđelović, András Perczel, László Buday, György Keserű, József Tímár","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In silico studies raised the possibility that farnesyltransferase inhibitors (FTIs) may have antitumoral effects on KRAS mutant cancer cells. Accordingly, we have tested FTIs (tipifarnib and lonafarnib) in G12C mutant human cancer cell lines in vitro and in vivo. We have discovered that the combination of the two drugs has a synergistic antitumoral effect. Next, we have tested FTIs on G12D mutant human cancer cell lines and found that the combination has antitumoral effect in various preclinical cancer models. At last, we have also tested FTIs on G12V mutant human cancer cells and again we have detected antitumoral effects. We suggest that FTIs may have clinical relevance outside the HRAS mutant cancers.</p>","PeriodicalId":94127,"journal":{"name":"Magyar onkologia","volume":"67 3","pages":"223-235"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}