Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3.

Show less

Author information

Affiliations

  • 1. Division of Molecular Carcinogenesis, Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
      Authors
    • Sun C 1
    • Prahallad A 1
    • Grernrum W 1
    • Tzani A 1
    • Schlicker A 1
    • Wessels LF 1
    • Halonen P 1
    • Lieftink C 1
    • Beijersbergen RL 1
    • Bernards R 1
    (10 authors)
  • 2. Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142 km 3.95, 10060 Candiolo, Torino, Italy.
      Authors
    • Hobor S 2
    • Cottino F 2
    (2 authors)
  • 3. Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142 km 3.95, 10060 Candiolo, Torino, Italy; Department of Oncology, University of Torino, Strada Provinciale 142 km 3.95, 10060 Candiolo, Torino, Italy.
      Authors
    • Bertotti A 3
    • Zecchin D 3
    • Galimi F 3
    • Trusolino L 3
    (4 authors)
  • 4. Division of Molecular Carcinogenesis, Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Biochemistry, The Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, QC H3G 1Y6, Canada.
      Authors
    • Huang S 4
    (1 author)
  • 5. Department of Pulmonary Diseases, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands.
      Authors
    • Smit EF 5
    (1 author)
    • Show all (8)

ORCIDs linked to this article

Show all (13)

Cell Reports, 27 Mar 2014, 7(1):86-93
https://doi.org/10.1016/j.celrep.2014.02.045 PMID: 24685132 

Abstract 

There are no effective therapies for the ~30% of human malignancies with mutant RAS oncogenes. Using a kinome-centered synthetic lethality screen, we find that suppression of the ERBB3 receptor tyrosine kinase sensitizes KRAS mutant lung and colon cancer cells to MEK inhibitors. We show that MEK inhibition results in MYC-dependent transcriptional upregulation of ERBB3, which is responsible for intrinsic drug resistance. Drugs targeting both EGFR and ERBB2, each capable of forming heterodimers with ERBB3, can reverse unresponsiveness to MEK inhibition by decreasing inhibitory phosphorylation of the proapoptotic proteins BAD and BIM. Moreover, ERBB3 protein level is a biomarker of response to combinatorial treatment. These data suggest a combination strategy for treating KRAS mutant colon and lung cancers and a way to identify the tumors that are most likely to benefit from such combinatorial treatment.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.celrep.2014.02.045

References 

Articles referenced by this article (29)

Show 10 more references (10 of 29)

Citations & impact 

Impact metrics

205
Citations
Jump to Citations

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/2216763
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/2216763

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1016/j.celrep.2014.02.045

Supporting
Mentioning
Contrasting
26
290
2

Article citations

Go to all (205) article citations

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.