Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (37906695)
Authors Ichikawa K, Ito S, Kato E, Abe N, Machida T, Iwasaki J, Tanaka G, Araki H, Wakayama K, Jona H, Sugimoto T, Miyadera K, Ohkubo S
Title TAS0612, a novel RSK, AKT, and S6K inhibitor, exhibits antitumor effects in preclinical tumor models.
Journal Vol Issue Date Pages Journal Short Title
Molecular cancer therapeutics 2023 Oct 31 Mol Cancer Ther
URL
Abstract Text The mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways are involved in cancer growth and survival; however, the clinical efficacy of single inhibitors of each pathway is limited or transient owing to resistance mechanisms, such as feedback signaling and/or re-expression of receptor-type tyrosine kinases (RTKs). This study identified a potent and novel kinase inhibitor, TAS0612, and characterized its properties. We found that TAS0612 is a potent, orally available compound that can inhibit p90RSK (RSK), AKT, and p70S6K (S6K) as a single agent and showed a strong correlation with the growth inhibition of cancer cells with PTEN loss or mutations, regardless of the presence of KRAS and BRAF mutations. Additional RSK inhibitory activity may differentiate the sensitivity profile of TAS0612 from that of signaling inhibitors that target only the PI3K pathway. Moreover, TAS0612 demonstrated broad-spectrum activity against tumor models wherein inhibition of MAPK or PI3K pathways was insufficient to exert antitumor effects. TAS0612 exhibited a stronger growth-inhibitory activity against the cancer cell lines and tumor models with dysregulated signaling with the genetic abnormalities described above than treatment with inhibitors against AKT, PI3K, MEK, BRAF, and EGFR/HER2. Additionally, TAS0612 demonstrated the persistence of blockade of downstream growth and anti-apoptotic signals, despite activation of upstream effectors in the signaling pathway and FoxO-dependent re-expression of HER3. In conclusion, TAS0612 with RSK/AKT/S6K inhibitory activity may provide a novel therapeutic strategy for cancer patients to improve clinical responses and overcome resistance mechanisms.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.