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Exceptional responders with invasive mucinous adenocarcinomas: a phase 2 trial of bortezomib in patients with KRAS G12D-mutant lung cancers
Open accessAbstract
KRAS G12D-mutant/p53-deficient non-small-cell lung cancer (NSCLC) models are dependent on the NF-κB pathway that can be down-regulated by the proteasome inhibitor bortezomib. Two exceptional responders were observed on prior clinical trials of bortezomib, both of whom had KRAS G12D-mutant NSCLC, prompting the initiation of this single-center phase 2 trial. Patients with advanced KRAS G12D-mutant NSCLC were eligible. Bortezomib was administered at 1.3 mg/m 2 subcutaneously (days 1, 4, 8, 11; 21-d cycle) until progression or unacceptable toxicity. The primary objective was best objective response (RECIST v1.1). Sixteen patients with KRAS G12D-mutant lung adenocarcinomas were treated. Patients had a median pack year smoking history of 4 (range 0–45). A partial response (PR) was observed in one patient (−66% from baseline) and stable disease in five patients on the first stage of this study (overall response rate of 6%, 95% CI: 0.2–30.2), and further patients were not accrued. The median progression-free survival was 1 mo (95% CI: 1–6). The median overall survival was 13 mo (95% CI: 6–NA). The most common treatment-related adverse events were fatigue (38%) and diarrhea (26%). TP53 status did not predict response on exploratory testing. Of note, the patient with a PR had a unique subtype of lung adenocarcinoma—invasive mucinous adenocarcinomas (IMA)—and had rapid clinical improvement and substantial disease regression, which was also previously observed in two other patients with advanced KRAS G12D-mutant lung cancer with IMAs who received bortezomib on separate clinical trials. Exceptional responses to bortezomib can be achieved in KRAS G12D-mutant NSCLCs. KRAS G12D mutation alone, however, is not a robust predictor of response. Further evaluation should only be performed after further elucidation of other factors such as co-occurring alterations and histologic subtype such as IMA that may predict sensitivity to therapy.
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Bortezomib monotherapy reached an objective response rate of 6% in patients with KRAS G12D-mutant lung cancer in a phase 2 clinical trial.
“bortezomib monotherapy reached an objective response rate of 6% in patients with KRAS G12D -mutant lung cancer in a phase 2 clinical trial. 41”
From Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer (2024) · cites this paper as [41]
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Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
Barbie, D. A., Tamayo, P., Boehm, J. S., Kim, S. Y., Moody, S. E., Dunn, I. F., Schinzel, A. C., Sandy, P., Meylan, E., Scholl, C., et al. (2009) · Nature · doi:10.1038/nature08460 · Cited by 3,922
Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs
Kris, M. G., Johnson, B. E., Berry, L. D., Kwiatkowski, D. J., Iafrate, A. J., Wistuba, I. I., Varella-Garcia, M., Franklin, W. A., Aronson, S. L., Su, P.-F., et al. (2014) · JAMA · doi:10.1001/jama.2014.3741 · Cited by 1,724
Self-citationNon-canonical NF-κB signaling pathway
Sun, S. (2010) · Cell Research · doi:10.1038/cr.2010.177 · Cited by 1,266
A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene
Luo, J., Emanuele, M. J., Li, D., Creighton, C. J., Schlabach, M. R., Westbrook, T. F., Wong, K.-K., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.05.006 · Cited by 1,017
Skoulidis, F., Byers, L. A., Diao, L., Papadimitrakopoulou, V. A., Tong, P., Izzo, J., Behrens, C., Kadara, H., Parra, E. R., Canales, J. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1236 · Cited by 936
Self-citationMoreau, P., Pylypenko, H., Grosicki, S., Karamanesht, I., Leleu, X., Grishunina, M., Rekhtman, G., Masliak, Z., Robak, T., Shubina, A., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70081-x · Cited by 920
Dogan, S., Shen, R., Ang, D. C., Johnson, M. L., D'Angelo, S. P., Paik, P. K., Brzostowski, E. B., Riely, G. J., Kris, M. G., Zakowski, M. F., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3265 · Cited by 639
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Self-citationYemelyanova, A. V., VANG, R. S., Kshirsagar, M. P., Lü, D., Marks, M. A., Shih, I., & Kurman, R. J. (2011) · Modern Pathology · doi:10.1038/modpathol.2011.85 · Cited by 514
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
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Self-citationSchabath, M. B., Welsh, E. A., Fulp, W. J., Chen, L., Teer, J. K., Thompson, Z., Engel, B. E., Xie, M., Berglund, A., Creelan, B., et al. (2015) · Oncogene · doi:10.1038/onc.2015.375 · Cited by 419
Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung
Shim, H. S., Kenudson, M. M., Zheng, Z., Liebers, M. R., Cha, Y. J., Ho, Q. V., Onozato, M. L., Le, L. P., Heist, R. S., & Iafrate, A. J. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000579 · Cited by 203
Prognostic Impact of KRAS Mutation Subtypes in 677 Patients with Metastatic Lung Adenocarcinomas
Yu, H. A., Sima, C. S., Shen, R., Kass, S. L., Gainor, J. F., Shaw, A. T., Hames, M. L., Iams, W. T., Aston, J. L., Lovly, C. M., et al. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000432 · Cited by 137
Self-citationResponse and Resistance to NF-κB Inhibitors in Mouse Models of Lung Adenocarcinoma
Xue, W., Meylan, E., Oliver, T. G., Feldser, D. M., Winslow, M. M., Bronson, R. T., & Jacks, T. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0073 · Cited by 131
Facchinetti, F., Bluthgen, M. V., Tergemina-Clain, G., Faivre, L., Pignon, J., Planchard, D., Remón, J., Soria, J., Lacroix, L., & Besse, B. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.08.002 · Cited by 109
Riely, G. J., Jordan, E., Kim, H. R., Yu, H. A., Berger, M. F., Solit, D. B., Kris, M. G., Ni, A., Arcila, M. E., & Ladanyi, M. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.9019 · Cited by 14
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Memon, D., Schoenfeld, A. J., Ye, D., Fromm, G. J., Rizvi, H. A., Zhang, X., Keddar, M. R., Mathew, D., Yoo, K. J., Qiu, J., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2023.12.013 · Cited by 227
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Zhou, C., Li, C., Luo, L., Li, X., Jia, K., He, N., Mao, S., Wang, W., Shao, C., Liu, X., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.06.001 · Cited by 102
Synthetic lethal strategies for the development of cancer therapeutics
Ngoi, N. Y. L., Gallo, D., Torrado, C., Nardo, M., Durocher, D., & Yap, T. A. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00966-z · Cited by 79
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Luo, J., Ostrem, J. M. L., Pellini, B., Imbody, D., Stern, Y. E., Solanki, H. S., Haura, E. B., & Villaruz, L. C. (2022) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_360354 · Cited by 46
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Zhang, C., Li, J., Tang, Q., Li, L., & Cao, D. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02472-x · Cited by 43
Tang, Y., Pu, X., Yuan, X., Pang, Z., Li, F., & Wang, X. (2024) · Cancer Gene Therapy · doi:10.1038/s41417-024-00778-4 · Cited by 38
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Bteich, F., Mohammadi, M., Li, T., Bhat, M. A., Sofianidi, A. A., Wei, N., & Kuang, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512030 · Cited by 34
Yarza, R., Bover, M., Agulló-Ortuño, M. T., & Docampo, L. C. I. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02010-9 · Cited by 33
Kim, M., Hwang, J., Kim, K., Hwang, S., Lee, H., Jung, J. Y., Lee, J. G., Cha, Y. J., & Shim, H. S. (2021) · Modern Pathology · doi:10.1038/s41379-021-00872-0 · Cited by 30
Laudisi, F., Grazia, A. D., Simone, V. D., Cherubini, F., Colantoni, A., Ortenzi, A., Franzè, E., Dinallo, V., Fusco, D. D., Monteleone, I., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.07.014 · Cited by 21
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Shoji, T., Kikuchi, E., Kikuchi, J., Takashima, Y., Furuta, M., Takahashi, H., Tsuji, K., Maeda, M., Kinoshita, I., Dosaka‐Akita, H., et al. (2020) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-020-04061-9 · Cited by 17
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Chua, A. D. W., Thaarun, T., Yang, H., & Lee, A. R. Y. B. (2023) · Health Science Reports · doi:10.1002/hsr2.1443 · Cited by 6
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Demir, T., Araz, M., Moloney, C., Hendem, E., Koçak, M. Z., Erman, M., Baş, O., Köstek, O., Sever, N., Karakaya, S., et al. (2024) · Clinical Lung Cancer · doi:10.1016/j.cllc.2024.05.004 · Cited by 6
Ferrara, M. G., Stefani, A., Pilotto, S., Carbone, C., Vita, E., Salvatore, M. D., D’Argento, E., Sparagna, I., Monaca, F., Valente, G., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.792385 · Cited by 4
Bang, E., Hwangbo, H., Kim, M. Y., Ji, S. Y., Kim, D. H., Shim, J., Moon, S., Kim, G., Cheong, J., & Choi, Y. H. (2023) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2023.104211 · Cited by 4
Torchiaro, E., Petti, C., Arena, S., Sassi, F. P., Migliardi, G., Mellano, A., Porporato, R., Basiricò, M., Gammaitoni, L., Berrino, E., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1130852 · Cited by 2
Setoguchi, K., Yanagi, S., Gi, T., Tsubouchi, H., Uto, K., Shigekusa, T., Matsumoto, N., Sato, Y. Z., & Nakazato, M. (2021) · American Journal of Case Reports · doi:10.12659/ajcr.932452
Mai, L., Yang, X., Shao, C., Yu, H., Du, F., Liu, J., Guan, Y., Li, H., Yang, M., Meng, H., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149083
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Searle, J., Menotti, M., McDaid, W. J., Baker, M. J., Chaturvedi, A., GINN, L. H., Reed, H., Carter, M., Blackhall, F. H., Lindsay, C. R., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08672-7
Chen, R., Zhu, H., Zhou, K., & Xie, J. (2026) · Experimental Cell Research · doi:10.1016/j.yexcr.2026.115154
Metadata
- Authors
- Drilon, A., Schoenfeld, A. J., Arbour, K. C., Litvak, A., Ni, A., Montecalvo, J., Yu, H. A., Panora, E., Ahn, L., Kennedy, M., Haughney-Siller, A., Miller, V., Ginsberg, M., Ladanyi, M., Arcila, M., Rekhtman, N., Kris, M. G., & Riely, G. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Molecular Case Studies
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2019-04
- Volume
- 5
- Issue
- 2
- Pages
- a003665
- ISSN
- 2373-2865 (ISSN-L)
- 2373-2873
- PMC
- PMC6549573
- OpenAlex
- W2931064118
- Cited by
- 31
- References
- 17
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 2
- Type
- posted content
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- Molecular Case Studies (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- American Society of Clinical Oncology
- National Cancer Institute (P30 P30CA008748, P30CA008748)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- KRAS G12D mutation, non-small cell lung cancer, lung adenocarcinoma, invasive mucinous adenocarcinoma, proteasome inhibitors, NF-κB signaling, p53 deficiency, exceptional responders, treatment response prediction, histological subtypes
- MeSH terms
- Bortezomib, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Adenocarcinoma, Mucinous, Carcinoma, Non-Small-Cell Lung, Female, Humans, Injections, Subcutaneous, Lung Neoplasms, Male, Middle Aged, Mutation, Prospective Studies, Proto-Oncogene Proteins p21(ras), Treatment Outcome
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