TY - JOUR AU - Filipovich, E. AU - Gorodkova, E. AU - Shcherbakova, A. AU - Asaad, W. AU - Popov, S. AU - Melnichenko, G. AU - Mokrysheva, N. AU - Utkina, M. TI - The role of cell cycle-related genes in the tumorigenesis of adrenal and thyroid neuroendocrine tumors JF - HELIYON J2 - HELIYON VL - 11 PY - 2025 IS - 1 SN - 2405-8440 DO - 10.1016/j.heliyon.2024.e41457 UR - https://m2.mtmt.hu/api/publication/35734075 ID - 35734075 N1 - Export Date: 3 February 2025 Correspondence Address: Utkina, M.; Laboratory of General, Russian Federation; email: mv.utkina@yandex.ru LA - English DB - MTMT ER - TY - JOUR AU - Ichimura, N. AU - Urata, Y. AU - Kobayashi, T. AU - Hibi, H. TI - Mutational landscape of oral mucosal melanoma based on comprehensive cancer genomic profiling tests in a Japanese cohort JF - ORAL ONCOLOGY J2 - ORAL ONCOL VL - 152 PY - 2024 SN - 1368-8375 DO - 10.1016/j.oraloncology.2024.106807 UR - https://m2.mtmt.hu/api/publication/35051167 ID - 35051167 N1 - Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School School of Medicine, Nagoya, Japan Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, Nagoya, Japan Export Date: 17 June 2024 CODEN: EJCCE Correspondence Address: Ichimura, N.; Department of Oral and Maxillofacial Surgery, 65 Tsurumai-cho, Showa-ku, Japan; email: norihisa@med.nagoya-u.ac.jp LA - English DB - MTMT ER - TY - JOUR AU - Krencz, Ildikó AU - Sztankovics, Dániel AU - Sebestyén, Anna AU - Pápay, Judit AU - Dankó, Titanilla AU - Moldvai, Dorottya AU - Lutz, Elmar AU - Khoor, Andras TI - RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 PG - 10 SN - 1219-4956 DO - 10.3389/pore.2024.1611593 UR - https://m2.mtmt.hu/api/publication/34805614 ID - 34805614 N1 - Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, United States Export Date: 17 June 2024 CODEN: POREF Correspondence Address: Khoor, A.; Department of Laboratory Medicine and Pathology, United States; email: khoor.andras@mayo.edu AB - RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy. LA - English DB - MTMT ER - TY - JOUR AU - Szalai, Fatime AU - Sztankovics, Dániel AU - Krencz, Ildikó AU - Moldvai, Dorottya AU - Pápay, Judit AU - Sebestyén, Anna AU - Khoor, Andras TI - Rictor—A Mediator of Progression and Metastasis in Lung Cancer JF - CANCERS J2 - CANCERS VL - 16 PY - 2024 IS - 3 PG - 16 SN - 2072-6694 DO - 10.3390/cancers16030543 UR - https://m2.mtmt.hu/api/publication/34545400 ID - 34545400 N1 - Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary Department of Laboratory Medicine and Pathology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, United States Cited By :1 Export Date: 17 June 2024 Correspondence Address: Khoor, A.; Department of Laboratory Medicine and Pathology, 4500 San Pablo Road, United States; email: khoor.andras@mayo.edu AB - Lung carcinoma is one of the most common cancer types for both men and women. Despite recent breakthroughs in targeted therapy and immunotherapy, it is characterized by a high metastatic rate, which can significantly affect quality of life and prognosis. Rictor (encoded by the RICTOR gene) is known as a scaffold protein for the multiprotein complex mTORC2. Among its diverse roles in regulating essential cellular functions, mTORC2 also facilitates epithelial–mesenchymal transition and metastasis formation. Amplification of the RICTOR gene and subsequent overexpression of the Rictor protein can result in the activation of mTORC2, which promotes cell survival and migration. Based on recent studies, RICTOR amplification or Rictor overexpression can serve as a marker for mTORC2 activation, which in turn provides a promising druggable target. Although selective inhibitors of Rictor and the Rictor-mTOR association are only in a preclinical phase, they seem to be potent novel approaches to reduce tumor cell migration and metastasis formation. Here, we summarize recent advances that support an important role for Rictor and mTORC2 as potential therapeutic targets in the treatment of lung cancer. This is a traditional (narrative) review based on Pubmed and Google Scholar searches for the following keywords: Rictor, RICTOR amplification, mTORC2, Rictor complexes, lung cancer, metastasis, progression, mTOR inhibitors. LA - English DB - MTMT ER - TY - JOUR AU - Sztankovics, Dániel AU - Szalai, Fatime AU - Moldvai, Dorottya AU - Dankó, Titanilla AU - Nagy, Noémi AU - Pápay, Judit AU - Khoór, András AU - Krencz, Ildikó AU - Sebestyén, Anna TI - Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression JF - EUROPEAN JOURNAL OF CELL BIOLOGY J2 - EUR J CELL BIOL VL - 103 PY - 2024 IS - 4 PG - 13 SN - 0171-9335 DO - 10.1016/j.ejcb.2024.151468 UR - https://m2.mtmt.hu/api/publication/35592130 ID - 35592130 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [TKP2021-EGA-24, NKFI-K-142799, NKFI-PD-146373]; University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund [UNKP-23-4-II-SE-9, 2024-2.1.1-EKOP-2024-00004]; Human Resource Development Operational Programme [EFOP-3.6.3-VEKOP-16-2017-00009] Funding text: Recent research at the Department of Pathology and Experimental Cancer Research (Semmelweis University, Budapest, Hungary) was funded by the National Research, Development and Innovation Office of Hungary [TKP2021-EGA-24 (A.S.) , NKFI-K-142799 (A.S.) , NKFI-PD-146373 (I.K.) ] . Our research was also supported by the University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund [UNKP-23-4-II-SE-9 (I.K.) , 2024-2.1.1-EKOP-2024-00004 (D.S., F.S., D.M.) ] and the Human Resource Development Operational Programme [EFOP-3.6.3-VEKOP-16-2017-00009 (F.S., D. M.) ] . LA - English DB - MTMT ER - TY - JOUR AU - Sztankovics, Dániel AU - Moldvai, Dorottya AU - Petővári, Gábor AU - Dankó, Titanilla AU - Szalai, Fatime AU - Miyaura, Risa AU - Varga, Viktória AU - Nagy, Noémi AU - Papp, Gergő AU - Pápay, Judit AU - Krencz, Ildikó AU - Sebestyén, Anna TI - mTOR hyperactivity and RICTOR amplification as targets for personalized treatments in malignancies JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 30 PY - 2024 PG - 19 SN - 1219-4956 DO - 10.3389/pore.2024.1611643 UR - https://m2.mtmt.hu/api/publication/34725263 ID - 34725263 N1 - Export Date: 17 June 2024 CODEN: POREF Correspondence Address: Sebestyén, A.; Department of Pathology and Experimental Cancer Research, Hungary; email: hsebanna@gmail.com AB - The increasing knowledge of molecular alterations in malignancies, including mutations and regulatory failures in the mTOR (mechanistic target of rapamycin) signaling pathway, highlights the importance of mTOR hyperactivity as a validated target in common and rare malignancies. This review summarises recent findings on the characterization and prognostic role of mTOR kinase complexes (mTORC1 and mTORC2) activity regarding differences in their function, structure, regulatory mechanisms, and inhibitor sensitivity. We have recently identified new tumor types with RICTOR (rapamycin-insensitive companion of mTOR) amplification and associated mTORC2 hyperactivity as useful potential targets for developing targeted therapies in lung cancer and other newly described malignancies. The activity of mTOR complexes is recommended to be assessed and considered in cancers before mTOR inhibitor therapy, as current first-generation mTOR inhibitors (rapamycin and analogs) can be ineffective in the presence of mTORC2 hyperactivity. We have introduced and proposed a marker panel to determine tissue characteristics of mTOR activity in biopsy specimens, patient materials, and cell lines. Ongoing phase trials of new inhibitors and combination therapies are promising in advanced-stage patients selected by genetic alterations, molecular markers, and/or protein expression changes in the mTOR signaling pathway. Hopefully, the summarized results, our findings, and the suggested characterization of mTOR activity will support therapeutic decisions. LA - English DB - MTMT ER -