Latest (92) Full Text Articles (6313) Focus on Liver Article Summary

MET inhibition in lung cancer Full Text
Translational Lung Cancer Research,  Review Article

Menis J. et al .– This paper aims to summarize data on Met biological function, on its interaction with cell signaling and other pathways and to present data on those Met inhibitors currently under evaluation. The discovery of new cancer–driver genes and the enforcement of molecules targeting them have changed the landscape of Non Small Cell Lung Cancer (NSCLC) treatment.As a matter of fact, the previous scenario of advanced NSCLC treatment has been completely revolutionized, switching from a “one size fits all” approach to a personalized therapy. It was concluded that Met can act as an ‘oncogene expedient’ even in absence of genetic alterations and might potentiate the effect of other oncogenes, promote malignant progression and participate in tumor angiogenesis. Met dysregulation correlates with disease prognosis in numerous cancers and represents a possible target for personalized treatment. The clinical efficacy of Met targeting agents in lung cancer needs further details from the ongoing trials as well as more information are necessary to establish the most appropriate diagnostic test to identify Met expression or amplification.

  • Met is a heterodimer receptor tyrosine kinase composed of a ?–chain and a ?–chain, linked by a disulphide bond.
  • Met was originally isolated as the product of a human oncogene, trp–met, in tumor cells treated with a chemical carcinogen.
  • Met gene encodes a 170–kD protein (p170met) that has constitutive and ligand–independent tyrosin–kinase activity.
  • Met has pivotal functions in embryogenesis and organogenesis of placenta, liver, kidney, neurons and muscles.
  • Moreover, in vivo, Met receptor activation determines a phenomenon called “invasive growth”, which includes cell proliferation, scattering, survival, motility and invasion, epithelial–mesenchymal transition and branched morphogenesis
  • In this scenario Met, a heterodimere receptor tyrosine kinase deeply involved into embryogenesis and organogenesis, has been introduced many years ago as a potential target for biological agents, becoming“druggable” only in this last period of time.
  • Met can be altered through receptor overexpression, genomic amplification, mutations or alternative splicing, autocrine or paracrine secretion of hepatic growth factor (HGF): these dysregulations stimulate tumorigenesis (in terms of cell–cell detachment, proliferation, invasion, angiogenesis and survival) and metastatization.
  • Met is overexpressed in lung cancer and Met gene amplification can drive the dependency of cell survival and proliferation upon the Met signaling. Both Met overexpression and amplification seem to correlate with poor prognosis.
  • Met amplification is also described to be linked to EGFR acquired resistance.
  • Several Met inhibitors have been tested both in preclinical and human trials, demonstrating activity in lung cancer treatment.
  • In patients with advanced NSCLC, a correct definition of the histotype is still the first step to design a proper therapeutic algorithm, but personalized molecular diagnosis is becoming more and more relevant.
  • Several molecules are currently under investigation and two of them already reached phase III trials in advanced NSCLC.

Please login or register to follow this author.
Are you sure you want to Unfollow this Author?
► Click here to access Full Text, PubMed, Publisher and related articles...
<< Previous Article | Next Article >>

Your Unread Messages in Oncology

See All >> Messages include industry-sponsored communications and special communications from MDLinx

Most Popular Oncology Articles

Last month's top read Top Articles of 2014

1 Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA) Journal of Clinical Oncology, May 29, 2014    Clinical Article

2 Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia New England Journal of Medicine, June 4, 2014    Evidence Based Medicine    Clinical Article

3 Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials The Lancet, March 25, 2014    Evidence Based Medicine    Clinical Article

4 A randomised phase II study of pemetrexed versus pemetrexed+erlotinib as second-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer European Journal of Cancer, May 23, 2014    Clinical Article

5 Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial The Lancet Oncology, March 7, 2014    Clinical Article

6 Survival of women with inflammatory breast cancer: A large population based study Annals of Oncology, April 16, 2014    Clinical Article

7 Coffee intake and gastric cancer risk Cancer Epidemiology, Biomarkers & Prevention, March 20, 2014    Clinical Article

8 Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline Journal of Clinical Oncology, May 5, 2014    Clinical Guideline

9 Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study The Lancet Oncology, May 27, 2014    Clinical Article

10 Radiotherapy of follicular lymphoma: updated role and new rules Current Treatment Options in Oncology, May 16, 2014    Clinical Guideline    Clinical Article

11 Adjuvant exemestane with ovarian suppression in premenopausal breast cancer New England Journal of Medicine, June 9, 2014    Evidence Based Medicine    Clinical Article

12 Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial The Lancet Oncology, May 27, 2014    Clinical Article

13 Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes of an open-label, non-inferiority, randomised controlled trial The Lancet Oncology, June 11, 2014    Clinical Article

14 Oral contraceptives, hormone replacement therapy and breast cancer risk: A cohort study of 16 928 women 48 years and older Acta Oncologica, May 22, 2014    Clinical Article

15 Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib New England Journal of Medicine, June 3, 2014    Evidence Based Medicine    Clinical Article

16 PEAK: A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer Journal of Clinical Oncology, May 9, 2014    Clinical Article

17 Exposure to infections and risk of leukemia in young children Cancer Epidemiology, Biomarkers & Prevention, May 6, 2014    Clinical Article

18 Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database Journal of Clinical Oncology, June 13, 2014    Clinical Article

19 Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort The Lancet Oncology, June 20, 2014    Clinical Article

20 Coffee intake and gastric cancer risk Cancer Epidemiology, Biomarkers & Prevention, March 11, 2014    Clinical Article

Indexed Journals in Oncology: Journal of Clinical Oncology, Cancer Research, Annals Oncologymore

Other Topics in Oncology

Register now to view all the MDLinx contents (FREE)!

  • Stay current on the latest literature, research and clinical news
  • Get special communications and offers from MDLinx and our sponsors
  • Receive invitations to paid market research
View Samples and Register

Connect with us, stay current.

Receive the latest mecial news
updates for free via email

Sign up!

Subscribe to our free RSS feeds:

Get the latest news in your specialty automatically added to your newsreader or your personal My Yahoo!, Google, My MSN or My AOL page. Learn More

Close