Reference Detail

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@jax.org

Ref Type Journal Article
PMID (22912816)
Authors Sun J, Sun Q, Brown MF, Dudgeon C, Chandler J, Xu X, Shu Y, Zhang L, Yu J
Title The multi-targeted kinase inhibitor sunitinib induces apoptosis in colon cancer cells via PUMA.
Journal Vol Issue Date Pages Journal Short Title
PloS one 7 8 2012 e43158 PLoS One
URL
Abstract Text Constitutive activation of pro-survival kinases has become a promising target of small molecules with an increasing interest in developing multi-targeted agents. The mechanisms underlying the responsiveness to most agents targeting cancer specific survival pathways are still poorly understood but critical for their clinical application. In this study, we found that sunitinib, a small molecule inhibitor of multiple tyrosine kinases including VEGFRs and PDGFRs induces apoptosis and inhibits cell growth in colon cancer cells in cell culture and xenograft models via the BH3-only protein PUMA. Sunitinib treatment induced PUMA transcription via the AKT/FoxO3a axis. PUMA, BH3 mimetics, or 5-Flurourical sensitized colon cancer cells to sunitinib-induced apoptosis. Furthermore, PUMA was induced by sunitinib treatment in xenograft tumors, and deficiency in PUMA significantly suppressed the anti-tumor effects of sunitinib. Our study suggests that PUMA-mediated apoptosis is important for the therapeutic responses to sunitinib, and activation of the mitochondrial pathway by BH3 mimetics or PUMA manipulation may be useful for improving the antitumor activity of sunitinib. Modulation of PUMA and selective Bcl-2 family members might be potential biomarkers for predicting sunitinib responses.

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.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References