OSI‐027 inhibits the tumorigenesis of colon cancer through mediation of c‐Myc/FOXO3a/PUMA axis

Lou, Jie; Lv, Jianxin; Zhang, Youping; Liu, Zhanju

doi:10.1002/cbin.11792

Cited by 7 publications

(1 citation statement)

References 36 publications

(46 reference statements)

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“…The results of multiple clinical trials showed that second-generation 'rapalogs' possess effective pharmacokinetic properties and exert anticancer effects (72). Table I provides a list of different types of mTORC2 inhibitors to treat CRC (73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84), liver cancer (85-99), gallbladder cancer (100)(101)(102), GC (61,(103)(104)(105)(106), esophageal cancer (32,(107)(108)(109)(110), pancreatic cancer (111)(112)(113)(114)(115)(116)(117)(118)(119) and biliary tract cancer (120)(121)(122)(123). The therapeutic efficacy of rapalogs may be diminished by the pro-survival feedback loops that may be induced by the rapalogs' mTORC1-specific inhibition, such as the PI3K-Akt and PI3K-RAS-ERK pathways.…”

Section: Targeted Therapymentioning

confidence: 99%

Roles of Rictor alterations in gastrointestinal tumors (Review)

Cao,

Guo,

Min

et al. 2024

Oncol Rep

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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.

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Section: Targeted Therapymentioning

confidence: 99%

Roles of Rictor alterations in gastrointestinal tumors (Review)

Cao,

Guo,

Min

et al. 2024

Oncol Rep

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mTORC2: A neglected player in aging regulation

Xu,

Chen,

Xiao

2024

Journal Cellular Physiology

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Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a pivotal role in various biological processes, through integrating external and internal signals, facilitating gene transcription and protein translation, as well as by regulating mitochondria and autophagy functions. mTOR kinase operates within two distinct protein complexes known as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), which engage separate downstream signaling pathways impacting diverse cellular processes. Although mTORC1 has been extensively studied as a pro‐proliferative factor and a pro‐aging hub if activated aberrantly, mTORC2 received less attention, particularly regarding its implication in aging regulation. However, recent studies brought increasing evidence or clues for us, which implies the associations of mTORC2 with aging, as the genetic elimination of unique subunits of mTORC2, such as RICTOR, has been shown to alleviate aging progression in comparison to mTORC1 inhibition. In this review, we first summarized the basic characteristics of mTORC2, including its protein architecture and signaling network. We then focused on reviewing the molecular signaling regulation of mTORC2 in cellular senescence and organismal aging, and proposed the multifaceted regulatory characteristics under senescent and nonsenescent contexts. Next, we outlined the research progress of mTOR inhibitors in the field of antiaging and discussed future prospects and challenges. It is our pleasure if this review article could provide meaningful information for our readers and call forth more investigations working on this topic.

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