The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer
Open accessAbstract
Combined targeting of KRAS-G12C, mTOR, and IGF1R enhances and extends the response to recently developed KRAS-G12C inhibitors in lung cancer models.
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“Still, in all cases, combination therapies to suppress adaptive feedback proved key to optimizing the frequency and durability of response in each tumor type (34,50,51).”
From Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition (2020) · cites this paper as [51]
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“other combinatorial partners including PI3K, mTOR, and Aurora Kinase inhibitors have been shown to have higher efficacy than EGFR inhibition in combination with KRAS G12C inhibition in lung cancer(10, 12, 13).”
From EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer. (2020) · cites this paper as [12]
Experimental — accuracy not yet measuredIn the citing paper
“Interestingly, the restoration of flux through the ERK pathway was similarly observed after ARS-1620 treatment, and the feedback activation of Ras upstream RTKs has been raised as one of the key mechanisms of resistance to ARS-1620.12,15”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [15]
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“These experiments have identified receptor tyrosine kinase (RTK) signaling to PI3K and mTOR (23, 37–40), as well as the autophagy pathway (30) as collateral dependencies with KRAS and MAPK pathway inhibitors.”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [38]
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Citations
Cites
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The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Targeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,354
Self-citationThe Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557
RAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943
Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
Bollag, G. E., Hirth, P., Tsai, J. Y., Zhang, J., Ibrahim, P. N., Cho, H., Spevak, W. R., Zhang, C., Zhang, Y., Habets, G. G. M., et al. (2010) · Nature · doi:10.1038/nature09454 · Cited by 1,875
RAS oncogenes: weaving a tumorigenic web
Pylayeva-Gupta, Y., Grabocka, E., & Bar-Sagi, D. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3106 · Cited by 1,789
Carracedo, A., Ma, L., Teruya-Feldstein, J., Rojo, F., Salmena, L., Alimonti, A., Egia, A., Sasaki, A. T., Thomas, G., Kozma, S. C., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34739 · Cited by 1,381
Engelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330
Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor
Janes, M. R., Zhang, J., Li, L.-S., Hansen, R., Peters, U., Guo, X., Chen, Y., Babbar, A., Firdaus, S. J., Darjania, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.006 · Cited by 1,172 · cited 5×
“To avoid toxicities associated with the presence of a MEK inhibitor in this triple combination, we substituted a KRAS-G12C inhibitor, ARS-1620 (20), for the MEK inhibitor.”
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KRAS Mutation: From Undruggable to Druggable in Cancer
Huang, L., Guo, Z., Wang, F., & Fu, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00780-4 · Cited by 1,127
RAS-targeted therapies: is the undruggable drugged?
Moore, A. R., Rosenberg, S. C., McCormick, F., & Malek, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0068-6 · Cited by 1,103
EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer.
Amodio, V., Yaeger, R., Arcella, P., Cancelliere, C., Lamba, S., Lorenzato, A., Arena, S., Montone, M., Mussolin, B., Bian, Y., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0187 · Cited by 504
“Besides RTK inhibition, several other combinatorial strategies have already been proposed, with the goal of potentiating the effects of these inhibitors(10-13).”
BackgroundVertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition
Ryan, M. B., Fece de la Cruz, F., Phat, S., Myers, D. T., Wong, E., Shahzade, H. A., Hong, C. B., & Corcoran, R. B. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3523 · Cited by 496
KRAS mutation in pancreatic cancer
Luo, J. (2021) · Seminars in Oncology · doi:10.1053/j.seminoncol.2021.02.003 · Cited by 360
Metadata
- Authors
- Molina-Arcas, M., Moore, C., Rana, S., van Maldegem, F., Mugarza, E., Romero-Clavijo, P., Herbert, E., Horswell, S., Li, L.-S., Janes, M. R., Hancock, D. C., & Downward, J.
- Affiliations
- Oncogene Biology, Francis Crick Institute, London NW1 1AT, UK.
- The Francis Crick Institute (GB)
- Institute of Cancer Research (GB)
- Royal Veterinary College (GB)
- Wellspring Biosciences (United States) (US)
- Corresponding author
- Downward, Julian
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2019-09-18
- Volume
- 11
- Issue
- 510
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC6764843
- OpenAlex
- W2973796265
- Semantic Scholar
- dca6223aaab20972c7583a0426e8b63dfc81d7f3
- Cited by
- 203
- References
- 55
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 27 · 2023: 32 · 2022: 36 · 2021: 51 · 2020: 24 · 2019: 3
- FWCI
- 20.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wellcome (103799/Z/14/Z, FC001070)
- H2020 European Research Council (RASTARGET)
- Medical Research Council (FC001070)
- Cancer Research UK (FC001070)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- KRAS G12C inhibitors, KRAS-mutant lung cancer, lung adenocarcinoma, combination therapy, MEK inhibition, IGF1R inhibition, mTOR inhibition, MAPK signaling, IGF1R signaling, tumor regression, mouse model
- MeSH terms
- Animals, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Cell Survival, Imidazoles, Lung Neoplasms, Mice, Nude, Mutation, Pyrazines, Pyridones, Pyrimidinones, Signal Transduction, Proto-Oncogene Proteins p21(ras), Receptor, IGF Type 1, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase Kinases, RNA, Small Interfering, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases
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