Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2023 Dec 26;12(12):2570-2575.
doi: 10.21037/tlcr-23-682. Epub 2023 Dec 22.

eIF4A dependency: the hidden key to unlock KRAS mutant non-small cell lung cancer's vulnerability

Silvia Casacuberta-Serra  1 , Iñigo Gonzalez-Larreategui  2 , Laura Soucek  1   2   3   4
Affiliations
Editorial

eIF4A dependency: the hidden key to unlock KRAS mutant non-small cell lung cancer's vulnerability

Silvia Casacuberta-Serra et al. Transl Lung Cancer Res. .
No abstract available

Keywords: KRAS; MYC; Non-small cell lung cancer (NSCLC); eukaryotic initiation factor-4A (eiF4A).

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-682/coif). S.C.S. reports that she received support from Spanish Ministry of Economy and Competitiveness [Proyectos de I+D+i en Líneas Estratégicas” (PLEC2021- 007959) grant]; she is the author of patents directly or indirectly connected to lung cancer treatment (EP20710558, EP22383031, EP23382345 and EP23382552); she is an employee and shareholder of Peptomyc S.L., a company that develops therapeutics for cancer treatment. I.G.L. reports that he received support from BBVA Foundation [2nd Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI-II) grant] and Spanish Ministry of Universities [Grant from the University Teacher Training Program FPU (FPU20/04812)] and he is the author of one patent connected to lung cancer treatment (EP23382552). L.S. reports that she received support from Spanish Ministry of Economy and Competitiveness [Proyectos de I+D+i en Líneas Estratégicas” (PLEC2021- 007959) grant], La Marató TV3 [grant (2019429)] and BBVA Foundation [2nd Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI-II) grant]; she is the CEO and shareholder of Peptomyc S.L., a company that develops therapeutics for cancer treatment, and received consulting fees from it; she is author of patents directly or indirectly connected to lung cancer treatment (EP13382167, EP16382339, EP19382195, EP19382194, EP22383031, EP22383028, EP23382345, EP23382552, EP23382553 and EP2338255). The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
The eIF4A is a relevant vulnerability in KRAS mutant NSCLC. In KRAS-driven tumors with high MYC levels, treatment with KRASi or MEKi induces a cytostatic response. This response is dependent on the balanced ratio between the apoptosis regulator BAX protein and the BCL-xL, as well as between the Bcl-2 homology 3-only protein Bim and the induced myeloid leukemia cell differentiation protein MCL1. However, combination therapy involving any of these inhibitors with an eIF4A inhibitor leads to reduced levels of BCL-xL and MCL1, which result in increased free BAX and Bim levels that trigger tumor apoptosis. Made with Biorender.com. KRASmut, KRAS-mutated; KRASi, KRAS inhibitor; MEKi, MEK inhibitor; eIF4A, eukaryotic initiation factor-4A; BCL-xL, B-cell lymphoma-extra-large molecule; NSCLC, non-small cell lung cancer.
See this image and copyright information in PMC

Comment on

Similar articles

See all similar articles

Cited by

References

    1. Dempke WC. Targeted Therapy for NSCLC--A Double-edged Sword? Anticancer Res 2015;35:2503-12. - PubMed
    1. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med 2020;383:1328-39. 10.1056/NEJMoa1917346 - DOI - PubMed
    1. Chmielewska I, Krawczyk P, Grenda A, et al. Breaking the 'Undruggable' Barrier: Anti-PD-1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer Patients with KRAS Mutations-A Comprehensive Review and Description of Single Site Experience. Cancers (Basel) 2023;15:3732. 10.3390/cancers15143732 - DOI - PMC - PubMed
    1. Yang Y, Zhang H, Huang S, et al. KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration. J Clin Med 2023;12:709. 10.3390/jcm12020709 - DOI - PMC - PubMed
    1. Farnsworth DA, Inoue Y, Johnson FD, et al. MEK inhibitor resistance in lung adenocarcinoma is associated with addiction to sustained ERK suppression. NPJ Precis Oncol 2022;6:88. 10.1038/s41698-022-00328-x - DOI - PMC - PubMed