JOURNAL ARTICLE
REVIEW
Add like
Add dislike
Add to saved papers

Back to the Bench? MEK and ERK Inhibitors for the Treatment of KRAS Mutant Lung Adenocarcinoma.

Current Medicinal Chemistry 2018 Februrary 14
BACKGROUND: Lung cancer accounts for one in five cancer deaths worldwide and mutations in the gene encoding for the Kirsten rat sarcoma (KRAS) oncoprotein define the largest molecular subset of non-small cell lung cancer (NSCLC). These tumors are characterized by activated MAPK signaling, however, no targeted inhibitors of mutant KRAS or of downstream signaling molecules have yet been approved for routine clinical use.

OBJECTIVE: The primary objective of this review is to critically summarize the current developmental state of MEK and ERK inhibitors in pre-clinical models and in human clinical trials for KRAS mutant lung cancer particularly in light of the newly emerging concept of immune checkpoint blockade.

METHOD: We performed a Pubmed-based literature search and considered publications from the fields of basic and translational biomedicinal and biochemistry research, as well as from past and ongoing human clinical trials (www.clinicaltrials.gov).

RESULTS AND CONCLUSIONS: MAPK pathway targeting agents are efficacious in pre-clinical models but their benefit is limited for patients with KRAS mutant NSCLC due to the lack of predictive factors, toxicity and the adaptive dynamic kinome reprogramming within the tumor. Overall, MEK inhibitors have advanced further in clinical development compared to ERK inhibitors. New treatment strategies as e.g. immune checkpoint blockade are currently revolutionizing the treatment paradigms and future clinical trials need to show if they replace MAPK targeting strategies or are used as add-on.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app