Phase I/II study of combined BCL-XL and MEK inhibition with navitoclax (N) and trametinib (T) in KRAS or NRAS mutant advanced solid tumours
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Combination treatments with navitoclax have been widely trialed in other in vivo strains and patients without major reported toxicities.
“combination treatments with navitoclax have been widely trialed in other in vivo strains and patients without major reported toxicities”
From Bcl-xL Is a Key Mediator of Apoptosis Following KRASG12C Inhibition in <i>KRASG12C</i> -mutant Colorectal Cancer (2023) · cites this paper as [49]
The Results report grade 3–4 treatment-related adverse events in 40% of the 43 patients, contrary to the claim that no major toxicities were reported. The paper describes a navitoclax–trametinib trial in patients and mentions tumour regressions in mouse models, but does not establish that navitoclax combinations were widely trialed across other strains and patients. (LLM, conf=0.87)
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KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?
Nagasaka, M., Li, Y., Sukari, A., Ou, S.-H. I., Al-Hallak, M. N., & Azmi, A. S. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.101974 · Cited by 185 · 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
Self-citationKhawaja, H., Briggs, R., Latimer, C. H., Rassel, M., Griffin, D., Hanson, L., Bardelli, A., Di Nicolantonio, F., McDade, S. S., Scott, C. J., et al. (2023) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-22-0301 · Cited by 12 · see citing works
“Although less well tolerated in our in vivo strain, combination treatments with navitoclax have been widely trialed in other in vivo strains and patients without major reported toxicities (46, 49).”
Background
- Authors
- Corcoran, R. B., Do, K. T., Cleary, J. M., Parikh, A. R., Yeku, O. O., Weekes, C. D., Veneris, J., Ahronian, L. G., Mauri, G., Van Seventer, E. E., Fetter, I. J., Gurski, J. M., Matulonis, U. A., Juric, D., Flaherty, K. T., Sullivan, R. J., Clark, J. W., Heist, R. S., & Shapiro, G. I.
- Affiliations
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 30
- Pages
- v164
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2978342037
- Cited by
- 17
- References
- 0
- Citations by year
- 2024: 3 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 3
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- navitoclax, trametinib, BCL-XL inhibition, MEK inhibition, KRAS mutation, NRAS mutation, RAS-mutant cancers, advanced solid tumors, combination therapy, dose escalation, building information modeling, synthetic lethality, colorectal cancer, pancreatic cancer, non-small cell lung cancer, gynecologic cancer, treatment-related adverse events, disease control rate
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