A bright future for KRAS inhibitors
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Acquired resistance may limit the efficacy of KRAS G12C inhibitors, which suggests that combination therapies may be needed.
“However, the initial enthusiasm has been somewhat tempered by work suggesting that acquired resistance may constrain the inhibitors’ efficacy, which indicates that combination therapies may be needed11–14.”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [12]
Cites
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 · see citing works
The Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour Immunity
Canon, J., Rex, K., Saiki, A. Y., Mohr, C., Cooke, K., Bagal, D., Gaida, K., Holt, T., Knutson, C. G., Koppada, N., et al. (2019) · Nature · doi:10.1038/s41586-019-1694-1 · Cited by 2,277 · see citing works
Planchard, D., Smit, E. F., Groen, H. J. M., Mazières, J., Besse, B., Helland, Å., Giannone, V., D'amelio, A. M., Zhang, P., Mookerjee, B., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30679-4 · Cited by 1,360 · see citing works
Hallin, J., Engstrom, L. D., Hargis, L., Calinisan, A., Aranda, R., Briere, D. M., Sudhakar, N., Bowcut, V., Baer, B. R., Ballard, J. A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1167 · Cited by 1,304 · see citing works
RAS Interaction with PI3K: More Than Just Another Effector Pathway
Castellano, E., & Downward, J. (2011) · Genes & Cancer · doi:10.1177/1947601911408079 · Cited by 762 · see citing works
Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design
Ostrem, J. M. L., & Shokat, K. M. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.139 · Cited by 641 · see citing works
Hosomi, Y., Morita, S., Sugawara, S., Kato, T., Fukuhara, T., Gemma, A., Takahashi, K., Fujita, Y., Harada, T., Minato, K., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.19.01488 · Cited by 482 · see citing works
Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1841 · Cited by 466 · see citing works
Fakih, M., O'Neil, B., Price, T. J., Falchook, G. S., Desai, J., Kuo, J., Govindan, R., Rasmussen, E., Morrow, P. K. H., Ngang, J., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.3003 · Cited by 172 · see citing works
Kras and tumor immunity: friend or foe?
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Self-citationMatikas, A., Mistriotis, D., Georgoulias, V., & Kotsakis, A. P. (2016) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2016.12.005 · Cited by 82 · see citing works
Sequist, L. V. D., Lee, J. S., Han, J., et al. (2019) · Cancer Research · doi:10.1158/1538-7445.am2019-ct033 · Cited by 18 · see citing works
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The metabolic landscape of RAS-driven cancers from biology to therapy
Mukhopadhyay, S., Vander Heiden, M. G., & McCormick, F. (2021) · Nature Cancer · doi:10.1038/s43018-021-00184-x · Cited by 315 · see citing works
KRAS: From undruggable to a druggable Cancer Target
Uprety, D., & Adjei, A. A. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102070 · Cited by 271 · see citing works
Strategies to tackle RAS-mutated metastatic colorectal cancer
Patelli, G., Tosi, F., Amatu, A., Mauri, G., Curaba, A., Patanè, D. A., Pani, A., Scaglione, F., Siena, S., & Sartore-Bianchi, A. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100156 · Cited by 86 · see citing works
Frank, K. J., Mulero-Sánchez, A., Berninger, A., Ruiz-Cañas, L., Bosma, A., Görgülü, K., Wu, N., Diakopoulos, K. N., Kaya-Aksoy, E., Ruess, D. A., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100815 · Cited by 40 · see citing works
Julian, C., Pal, N., Gershon, A., Evangelista, M., Purkey, H., Lambert, P., Shi, Z., & Zhang, Q. (2023) · BMC Cancer · doi:10.1186/s12885-023-10778-6 · Cited by 31 · see citing works
The Research Progress of Direct KRAS G12C Mutation Inhibitors
Yang, A., Li, M., & Fang, M. (2021) · Pathology and Oncology Research · doi:10.3389/pore.2021.631095 · Cited by 15 · see citing works
“Clinical Application of MRTX849 The preliminary results of a phase I/II trial, which began in January 2019, were first presented at the AACR-NCI-EORTC Conference in 2019 (International Conference on Molecular Targets and Cancer Therapy) [27].”
Background
- Authors
- Bar-Sagi, D., Knelson, E. H., & Sequist, L. V.
- Affiliations
- Harvard University (US)
- Corresponding author
- Sequist, Lecia V.
- Venue
- Nature Cancer
- Published
- 2020-01-13
- Volume
- 1
- Issue
- 1
- Pages
- 25-27
- ISSN
- 2662-1347 (ISSN-L)
- OpenAlex
- W2999746123
- Cited by
- 74
- References
- 12
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 3 · 2023: 14 · 2022: 15 · 2021: 20 · 2020: 13
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- KRAS inhibitors, KRAS G12C, KRAS mutation, small molecule inhibitors, targeted cancer therapy, clinical trials
- MeSH terms
- Humans, Lung Neoplasms, Mutation, Proto-Oncogene Proteins p21(ras)
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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