Skip to main content
  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Highlights

Highlights of This Issue

DOI:  Published April 2012
  • Article
  • Info & Metrics
  • PDF
Loading

Combinations Overcome Acquired Resistance to BRAF Inhibition

Greger et al. Page 909

BRAF inhibitors have shown clinical benefit; however, resistance eventually occurs. To identify determinants of resistance and new treatments, Greger and colleagues isolated dabrafenib-resistant BRAF mutant melanoma clones and found that NRAS or MEK1 mutations contribute to BRAF inhibitor resistance. Treatment with dabrafenib and the MEK inhibitor trametinib inhibited proliferation and decreased MEK-ERK signaling of these clones. In addition, the resistant clones responded to the combination of a PI3K/mTOR inhibitor with dabrafenib or trametinib. Clinical trials are in progress to evaluate the genetic mutations and test combinations in patients that progress after BRAF inhibitor treatment and in BRAF inhibitor treatment of naive patients.

A Melanoma-Specific Mutation Panel

Dutton-Regester et al. Page 888

Significant success with molecular-based targeted drugs has recently been achieved in metastatic melanoma; however, the success of these drugs is dependent on the presence or absence of mutations within the patient's tumor that can confer drug efficacy or resistance. For this reason, Dutton-Regester and colleagues have developed a high-throughput, sensitive, cost-effective mutation panel for the identification of frequently occurring and clinically relevant mutations in melanoma. When used in a clinical setting, this panel may rapidly and accurately identify potentially effective treatment strategies using novel or existing molecular-based targeted drugs.

CEP-32496, Potent and Efficacious BRAF Inhibitor

James et al. Page 930

CEP-32496, a functionally selective BRAF inhibitor, exhibits selective cytotoxicity for BRAFV600E versus wildtype cells and is bioavailable and active against BRAFv600E xenografts in mice. James and colleagues describe that while like clinically tested BRAF inhibitors CEP-32496 did not inhibit cellular CRAF, it targets other kinases of interest and did not cause hyperplasia with repeat high-dose administration in nonclinical species. The balance of kinase inhibition and tolerability makes CEP-32496 an important new clinical tool, as these properties promise to both provide multiple routes of pathway inhibition and to mitigate against hyperplastic side effects previously observed with selective BRAF inhibitors.

HGF Nanobody Therapy in Nude Mice

Vosjan et al. Page 1017

Hepatocyte growth factor (HGF) is associated with tumor aggressiveness and poor prognosis. We report the development of therapeutic anti-HGF Nanobodies and their potential for PET imaging of HGF expression. Nanobodies radiolabeled with the PET isotope zirconium-89 showed selective tumor targeting in xenograft-bearing mice. In a therapy study using repeated doses of 10, 30 or 100 μg/mouse, all Nanobody-treated mice showed tumor growth delay compared to the control group. In the 100 μg group, 4 out of 6 mice were cured. These results show that HGF Nanobodies have potential for therapy and for assessment of HGF expressing with PET.

  • ©2012 American Association for Cancer Research.
PreviousNext
Back to top
Molecular Cancer Therapeutics: 11 (4)
April 2012
Volume 11, Issue 4
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Cancer Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Highlights of This Issue
(Your Name) has forwarded a page to you from Molecular Cancer Therapeutics
(Your Name) thought you would be interested in this article in Molecular Cancer Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Highlights of This Issue
Mol Cancer Ther April 1 2012 (11) (4) 793;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Highlights of This Issue
Mol Cancer Ther April 1 2012 (11) (4) 793;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Combinations Overcome Acquired Resistance to BRAF Inhibition
    • A Melanoma-Specific Mutation Panel
    • CEP-32496, Potent and Efficacious BRAF Inhibitor
    • HGF Nanobody Therapy in Nude Mice
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Selected Articles from This Issue
  • Selected Articles from This Issue
  • Selected Articles from This Issue
Show more Highlights
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About MCT

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Molecular Cancer Therapeutics
eISSN: 1538-8514
ISSN: 1535-7163

Advertisement