The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Obstruction of BRAFV600E transcription by complementary PNA oligomers as a means to inhibit BRAF-mutant melanoma growth
Abstract
Peptide nucleic acid (PNA) oligomers are DNA mimics, which are capable of binding gene sequences 1000-fold more avidly than complementary native DNA by strand invasion and effectively obstruct transcription. Irreversibly obstructing the transcription or replication of a gene sequence, such as BRAF V600E, offers a potential route to specifically target the cancer cell itself. We have employed PNA oligomers to target BRAF V600E in a sequence-specific complementary manner. These PNAs have been modified by appending configurationally stabilizing cationic peptides in order to improve their cellular delivery and target avidity. Our results indicate that exposure of the melanoma cell lines to a modified PNA-peptide conjugate complementary to BRAF V600E mutation sequence results in a concentration-dependent and time-dependent inhibition of cell growth that is specific for the BRAF V600E-mutant melanoma cell lines with inhibition of mRNA and protein expression. Xenograft mouse trials show increased tumor growth delay and necrosis with the BRAF V600E-complementary PNA-peptide conjugates as compared with the saline and scrambled PNA sequence controls. Similarly, quantitative measurement shows a 2.5-fold decrease in Ki67 and a 3-fold increase in terminal deoxynucleotidyl transferase dUTP nick end labeling expression with this approach. PNA-delivery peptide conjugates represent a novel way to target BRAF V600E and represent a new approach in targeting selective oncogenes that induce tumor growth.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PNAs have the advantage of being highly sequence-selective, enabling the targeting of mutant alleles while sparing the wildtype.
“PNAs have the advantage of being highly sequence-selective, enabling the targeting of mutant alleles while sparing the wildtype [72].”
From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [72]
Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,318
Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib
Robert, C., Karaszewska, B., Schachter, J., Rutkowski, P. L., Mackiewicz, A. A., Stroyakovskiy, D., Lichinitser, M., Dummer, R., Grange, F., Mortier, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1412690 · Cited by 2,763
Combined Vemurafenib and Cobimetinib in BRAF -Mutated Melanoma
Larkin, J., Ascierto, P. A., Dréno, B., Atkinson, V. G., Liszkay, G., Maio, M., Mandalà, M., Демидов, Л. В., Stroyakovskiy, D., Thomas, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408868 · Cited by 2,115
Sharma, P., Retz, M. M., Siefker-Radtke, A. O., Baron, A. D., Necchi, A., Bedke, J., Plimack, E. R., Vaena, D. A., Grimm, M., Sergio Bracarda, A., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30065-7 · Cited by 1,746
Long, G. V., Stroyakovskiy, D., Gogas, H. J., Levchenko, E., de Braud, F., Larkin, J., Garbe, C., Jouary, T., Hauschild, A., Grob, J., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60898-4 · Cited by 1,435
Fmoc Solid Phase Peptide Synthesis
Chan, W. C., & White, P. D. (1999) · doi:10.1093/oso/9780199637256.001.0001 · Cited by 691
D’Angelo, S. P., Larkin, J., Sosman, J. A., Lebbé, C., Brady, B., Neyns, B., Schmidt, H., Hassel, J. C., Hodi, F. S., Lorigan, P. C., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.9258 · Cited by 653
Peptide Nucleic Acids (PNA): Synthesis, properties and potential applications
Hyrup, B., & Nielsen, P. E. (1996) · Bioorganic & Medicinal Chemistry · doi:10.1016/0968-0896(95)00171-9 · Cited by 488
Larkin, J., Lao, C. D., Urba, W. J., McDermott, D. F., Horak, C., Jiang, J., & Wolchok, J. D. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.1184 · Cited by 223
Strand-invasion of duplex DNA by peptide nucleic acid oligomers.
Peffer, N. J., Hanvey, J. C., Bisi, J., Thomson, S. A., Hassman, C. F., Noble, S. A., & Babiss, L. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10648 · Cited by 174
Kidney injuries related to ipilimumab
Izzedine, H., Gueutin, V., Gharbi, C., Mateus, C., Robert, C., Routier, É., Thomas, M., Baumelou, A., & Rouvier, P. (2014) · Investigational New Drugs · doi:10.1007/s10637-014-0092-7 · Cited by 170
Peptide nucleic acid (PNA) binding-mediated induction of human -globin gene expression
Wang, G., Xu, X., Pace, B. S., Dean, D. A., Glazer, P. M., Chan, P., Goodman, S. R., & Shokolenko, I. N. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.13.2806 · Cited by 105
Tonelli, R., Purgato, S., Camerin, C., Fronza, R., Bologna, F., Alboresi, S., Franzoni, M., Corradini, R., Sforza, S., Faccini, A., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-04-0213 · Cited by 91
Acute visual loss after ipilimumab treatment for metastatic melanoma
Wilson, M. A., Guld, K., Galetta, S. L., Walsh, R. D., Kharlip, J., Tamhankar, M. A., McGettigan, S., Schuchter, L. M., & Fecher, L. A. (2016) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0170-9 · Cited by 73
Strand invasion by mixed base PNAs and a PNA-peptide chimera
Zhang, X. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.17.3332 · Cited by 73
PNA-Dependent Gene Chemistry: Stable Coupling of Peptides and Oligonucleotides to Plasmid DNA
Zelphati, O., Liang, X., Nguyen, C., BARLOW, S., Sheng, S., Shao, Z., & Felgner, P. L. (2000) · BioTechniques · doi:10.2144/00282rr01 · Cited by 61
Weber, J. S. (2012) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2012.32.79 · Cited by 57
Cutrona, G., Carpaneto, E. M., Ponzanelli, A., Ulivi, M., Millo, E., Scarfı̀, S., Roncella, S., Benatti, U., Boffa, L. C., & Ferrarini, M. (2003) · PubMed · Cited by 38
Cogoi, S., Codognotto, A., Rapozzi, V., Meeuwenoord, N. J., van der Marel, G., & Xodo, L. E. (2005) · Biochemistry · doi:10.1021/bi0505215 · Cited by 36
The T1799A point mutation is present in posterior uveal melanoma
Janssen, C. S., Sibbett, R., Henriquez, F. L., McKay, I. C., Kemp, E., & Roberts, F. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604731 · Cited by 33
Chaubey, B., Tripathi, S., & Pandey, V. N. (2008) · Oligonucleotides · doi:10.1089/oli.2007.0088 · Cited by 30
Novel Targeted Therapies for Metastatic Melanoma
Iams, W. T., Sosman, J. A., & Chandra, S. (2017) · The Cancer Journal · doi:10.1097/ppo.0000000000000242 · Cited by 28
Yu, X., Ambrosini, G., Roszik, J., Eterovic, A. K., Stemke‐Hale, K., Seftor, E. A., Chattopadhyay, C., Grimm, E. A., Carvajal, R. D., Hendrix, M. J. C., et al. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12345 · Cited by 26
Self-citationBRAF V600E-dependent role of autophagy in uveal melanoma
Zhao, Y., Wang, W., Min, I., Wyrwas, B., Moore, M., Zarnegar, R., & Fahey, T. J. (2017) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-016-2317-y · Cited by 26
BRAF V600 mutations in Langerhans cell histiocytosis with a simple and unique assay
Tatsuno, M., Shioda, Y., Iwafuchi, H., Yamazaki, S., Iijima, K., Takahashi, C., Ono, H., Uchida, K., Okamura, O., Matubayashi, M., et al. (2016) · Diagnostic Pathology · doi:10.1186/s13000-016-0489-z · Cited by 13
Flagged first, then by citations
Cited by
Sorted by citations
KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance
Ash, L. J., Busia-Bourdain, O., Okpattah, D., Kamel, A., Liberchuk, A., & Wolfe, A. L. (2024) · Current Oncology · doi:10.3390/curroncol31040150 · Cited by 68
“The avidity of PNAs for a single strand of”
BackgroundFunctions of MAP3Ks in antiviral immunity
Guan, J., Fan, Y., Wang, S., & Zhou, F. (2023) · Immunologic Research · doi:10.1007/s12026-023-09401-4 · Cited by 30
Shigeto, H., Miyata, H., Ashizawa, T., Iizuka, A., Kikuchi, Y., HOZUMI, C., Maeda, C., Yamaguchi, K. D., Yamamura, S., & Akiyama, Y. (2023) · Cancer Genomics & Proteomics · doi:10.21873/cgp.20389 · Cited by 3
Targeting Oncogenic KRAS Using Peptide Nucleic Acid Oligomers Attached to Cell-Penetrating Peptides
Mondal, J., Lam, D., Alcindor, T. O., Gerritsen, M. E., Brotz, T. M., Kennedy, J., Rehlaender, B., Ross, A. J., Levy, D. E., Bonagura, C. A., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27167158 · Cited by 1
Self-citationMondal, J., Lam, D., Gerritsen, M. E., Brotz, T. M., Kennedy, J. G., Rehlaender, B., Ross, A. J., Levy, D. E., Bonagura, C. A., Lanzilotta, W. N., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.28.645837
Self-citation
Metadata
- Authors
- Rothman, J. H., Surriga, O., de Stanchina, E., Vasudeva, S. D., & Schwartz, G. K.
- Affiliations
- Columbia University Irving Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Rothman, J H
- Venue
- Cancer Gene Therapy
- Published
- 2017-09
- Volume
- 24
- Issue
- 9
- Pages
- 401-408
- ISSN
- 0929-1903 (ISSN-L)
- 1476-5500
- OpenAlex
- W2758489627
- Cited by
- 4
- References
- 26
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Society of Clinical Oncology
- Memorial Sloan-Kettering Cancer Center
- National Cancer Institute (P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- peptide nucleic acid, PNA oligomers, BRAF V600E mutation, melanoma, transcriptional inhibition, PNA-peptide conjugates, cationic peptides, oncogene targeting, tumor growth inhibition, xenograft tumor model, Ki-67, apoptosis
- MeSH terms
- Animals, Female, Humans, Melanoma, Mice, Nude, Transcription, Genetic, Amino Acid Substitution, Mutation, Missense, Peptide Nucleic Acids, Xenograft Model Antitumor Assays, Proto-Oncogene Proteins B-raf, Mice
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
