Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer

Joechle, Katharina; Guenzle, Jessica; Hellerbrand, Claus; Strnad, Pavel; Cramer, Thorsten; Neumann, Ulf; Lang, Sven A.

doi:10.4251/wjgo.v13.i11.1632

Cited by 6 publications

(3 citation statements)

References 112 publications

(141 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the well-known oncogenic alterations of the mTOR pathway is the RICTOR amplification, which has been shown to contribute to progression and metastasis in certain cancers through its association with the molecular signaling behind these processes (e.g., Wnt/β-katenin, MAPK/ERK pathways) [41]. Several studies have demonstrated both RICTOR amplification and Rictor overexpression in different types of cancer, including lung cancer [9,17,[42][43][44][45][46][47]. Moreover, both RICTOR amplification and Rictor overexpression have been identified to be associated with poor prognosis and shorter survival [17,28,48].…”

Section: Rictor-mtor Association-the Mtorc2 Protein Complex and Its F...mentioning

confidence: 99%

Rictor—A Mediator of Progression and Metastasis in Lung Cancer

Szalai,

Sztankovics,

Krencz

et al. 2024

Cancers

View full text Add to dashboard Cite

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.

show abstract

Section: Rictor-mtor Association-the Mtorc2 Protein Complex and Its F...mentioning

confidence: 99%

Rictor—A Mediator of Progression and Metastasis in Lung Cancer

Szalai,

Sztankovics,

Krencz

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

“…Additionally, higher Rictor expression has been described in several tumor types, including lung [ 56 ], esophageal [ 57 ], breast [ 58 ], pancreatic [ 59 ], liver [ 60 ], and melanoma [ 61 ], where high Rictor expression was associated with poorer prognosis and shorter survival [ 55 ]. Table 1 summarizes mTORC2 hyperactivity and/or RICTOR amplification in different tumor types.…”

Section: Overexpression Of the Rictor Protein And The Associated Incr...mentioning

confidence: 99%

mTOR hyperactivity and RICTOR amplification as targets for personalized treatments in malignancies

Sztankovics,

Moldvai,

Petővári

et al. 2024

Pathol. Oncol. Res.

View full text Add to dashboard Cite

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.

show abstract

“…Inhibition of mTORC1/mTORC2 reduced tumor metastasis, but the inhibition of mTORC1 alone by rapamycin exerted no effect on tumor metastasis ( 57 ). Dual inhibition of mTORC1/mTORC2 by OSI027 reversed the high expression of MDR1 in adriamycin-induced liver cancer, thereby improving the sensitivity of cancer cells to adriamycin ( 58 ).…”

Section: Effects Of Rictor In Gastrointestinal Cancersmentioning

confidence: 99%

Roles of Rictor alterations in gastrointestinal tumors (Review)

Cao,

Guo,

Min

et al. 2024

Oncol Rep

View full text Add to dashboard Cite

Gastrointestinal tumors account for five of the top 10 causes of mortality from all cancers (colorectal, liver, stomach, esophageal and pancreatic cancer). Mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in various human cancers. As a core component of the mTOR complex 2 (mTORC2), Rictor is a key effector molecule of the PI3K/Akt pathway. A high alteration rate of Rictor has been observed in gastrointestinal tumors, and such Rictor alterations are often associated with resistance to chemotherapy and related adverse clinical outcomes. However, the exact roles of Rictor in gastrointestinal tumors remain elusive. The aim of the present study was to critically discuss the following: i) Mutation and biological characteristics of Rictor in tumors with a detailed overview of Rictor in cell proliferation, angiogenesis, apoptosis, autophagy and drug resistance; ii) the role of Rictor in tumors of the digestive system, particularly colorectal, hepatobiliary, gastric, esophageal and pancreatic cancer and cholangiocarcinoma; and iii) the current status and prospects of targeted therapy for Rictor by inhibiting Akt activation. Despite the growing realization of the importance of Rictor/mTORC2 in cancer, the underlying mechanistic details remain poorly understood; this needs to change in order for the development of efficient targeted therapies and re-sensitization of therapy-resistant cancers to be made possible.

show abstract

Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer

Cited by 6 publications

References 112 publications

Rictor—A Mediator of Progression and Metastasis in Lung Cancer

Rictor—A Mediator of Progression and Metastasis in Lung Cancer

mTOR hyperactivity and RICTOR amplification as targets for personalized treatments in malignancies

Roles of Rictor alterations in gastrointestinal tumors (Review)

Contact Info

Product

Resources

About