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 (25759019)
Authors Sharpe HJ, Pau G, Dijkgraaf GJ, Basset-Seguin N, Modrusan Z, Januario T, Tsui V, Durham AB, Dlugosz AA, Haverty PM, Bourgon R, Tang JY, Sarin KY, Dirix L, Fisher DC, Rudin CM, Sofen H, Migden MR, Yauch RL, de Sauvage FJ
Title Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma.
Journal Cancer cell
Vol 27
Issue 3
Date 2015 Mar 9
URL
Abstract Text Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (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 a longer phrase which contains spaces "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
ATR T2516I missense unknown ATR T2516I lies within the PI3K/PI4K domain of the Atr protein (UniProt.org). T2516I has been identified in sequencing studies (PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Atr protein function is unknown (PubMed, Nov 2020).
PIK3CA P449L missense unknown PIK3CA P449L lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P449L has been identified in sequencing studies (PMID: 29032825, PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2021).
PIK3CA P466S missense unknown PIK3CA P466S lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P466S has been identified in sequencing studies (PMID: 25759019, PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2021).
ROS1 E2308K missense unknown ROS1 E2308K lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). E2308K has been identified in sequencing studies (PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Feb 2021).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References