RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients
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// Talia Golan 1 , Elina Zorde Khvalevsky 2 , Ayala Hubert 3 , Rachel Malka Gabai 2 , Naama Hen 2 , Amiel Segal 4 , Abraham Domb 5 , Gil Harari 6 , Eliel Ben David 7 , Stephen Raskin 1 , Yuri Goldes 1 , Eran Goldin 8 , Rami Eliakim 1 , Maor Lahav 1 , Yael Kopleman 9 , Alain Dancour 8 , Amotz Shemi 2 and Eithan Galun 10 1 The Sackler School of Medicine, The Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel 2 Silenseed Ltd., Jerusalem, Israel 3 Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 4 The Gastroenterology Institute, Shaare Zedek Medical Centre, Jerusalem, Israel 5 Institute of Drug Research, School of Pharmacy-Faculty of Medicine, Center for Nanoscience and Nanotechnology and The Alex Grass Centre for Drug Design and Synthesis, The Hebrew University of Jerusalem, Jerusalem, Israel 6 MediStat Ltd., Jerusalem, Israel 7 Hadassah-Hebrew University Medical Centre, Jerusalem, Israel 8 The Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel 9 Gastroenterology Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel 10 The Goldyne Savad Institute for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel Correspondence to: Talia Golan, email: // Keywords : Pancreatic cancer, KRAS, overall survival, siRNA, polymer implant Received : March 04, 2015 Accepted : May 02, 2015 Published : May 19, 2015 Abstract Purpose: The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC). Methods: An open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs , in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODER TM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death. Results: Fifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%. Conclusions: The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785
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In a clinical trial involving siG12D-LODER in combination with chemotherapy, promising outcomes were observed, including inhibited tumor growth, reduced metastasis development and improved survival rates in patients with locally advanced PDAC.
“Furthermore, in a clinical trial involving siG12D-LODER, a sustained release siRNA matrix, in combination with chemotherapy, promising outcomes were observed, including inhibited tumor growth, reduced metastasis development and improved survival rates in patients with locally advanced PDAC [106].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [106]
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Experimental — accuracy not yet measuredsiG12D-LODER has shown potential in a phase I trial of combined chemotherapy in 12 patients with PDAC.
“It has shown its potential in phase I trial of combined chemotherapy in 12 patients with PDAC [93].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [93]
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FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., Adenis, A., Raoul, J.-L., Gourgou-Bourgade, S., de la Fouchardière, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011923 · Cited by 7,810 · see citing works
Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S. A., Ma, W. W., Saleh, M. N., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1304369 · Cited by 6,712 · see citing works
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
Iacobuzio-Donahue, C. A., Fu, B., Yachida, S., Luo, M., Abe, H., Henderson, C. M., Vilardell, F., Wang, Z., Keller, J. W., Banerjee, P., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.7188 · Cited by 1,081 · see citing works
Singh, A., Greninger, P., Rhodes, D., Koopman, L., Violette, S., Bardeesy, N., & Settleman, J. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.022 · Cited by 841 · see citing works
Loehrer, P. J., Feng, Y., Cardenes, H. R., Wagner, L. I., Brell, J. M., Cella, D. F., Flynn, P. J., Ramanathan, R. K., Crane, C. H., Alberts, S. R., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.8904 · Cited by 831 · see citing works
Chauffert, B., Mornex, F., Bonnetain, F., Rougier, P. R., Mariette, C., Bouché, O., Bosset, J.-F., Aparicio, T., Mineur, L., Azzedine, A., et al. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn281 · Cited by 696 · see citing works
Kinetics of interaction of nucleotides with nucleotide-free H-ras p21
John, J., Sohmen, R., Feuerstein, J., Linke, R., Wittinghofer, A., & Goody, R. S. (1990) · Biochemistry · doi:10.1021/bi00477a025 · Cited by 429 · see citing works
Kim, S. H., Jeong, J. H., Hyeon, L. S., Kim, S. W., & Park, T. G. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.03.008 · Cited by 362 · see citing works
Mutant KRAS is a druggable target for pancreatic cancer
Zorde Khvalevsky, E., Gabai, R., Rachmut, I. H., Horwitz, E., Brunschwig, Z., Orbach, A., Shemi, A., Golan, T., Domb, A. J., Yavin, E., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314307110 · Cited by 295 · see citing works
Self-citationRNAi Therapies: Drugging the Undruggable
Wu, S. Y., Lopez‐Berestein, G., Călin, G. A., & Sood, A. K. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008362 · Cited by 273 · see citing works
Molecular genetics of pancreatic intraepithelial neoplasia
Feldmann, G., Beaty, R., Hruban, R. H., & Maitra, A. (2007) · Journal of Hepato-Biliary-Pancreatic Surgery · doi:10.1007/s00534-006-1166-5 · Cited by 269 · see citing works
Blazer, M. A., Wu, C. S.-Y., Goldberg, R. M., Phillips, G. S., Schmidt, C. R., Muscarella, P., Wuthrick, E. J., Williams, T. M., Reardon, J., Ellison, E. C., et al. (2014) · Annals of Surgical Oncology · doi:10.1245/s10434-014-4225-1 · Cited by 243 · see citing works
Herman, J. M., Wild, A. T., Wang, H., Tran, P. T., Chang, K. J., Taylor, G., Donehower, R. C., Pawlik, T. M., Ziegler, M. A., Cai, H., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.7516 · Cited by 186 · see citing works
Fleming, J. B., Shen, G.-L., Holloway, S. E., Davis, M., & Brekken, R. A. (2005) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-04-0206 · Cited by 176 · see citing works
Ziske, C. G., Schlie, C., Gorschlüter, M., Glasmacher, A. G., Mey, U., Strehl, J., Sauerbruch, T., & Schmidt‐Wolf, I. G. H. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601263 · Cited by 168 · see citing works
Genetic and Epigenetic Alterations in Pancreatic Carcinogenesis
Delpu, Y., Hanoun, N., Lulka, H., Sicard, F., Sèlves, J., Buscail, L., Torrisani, J., & Cordelier, P. (2011) · Current Genomics · doi:10.2174/138920211794520132 · Cited by 123 · see citing works
Réjiba, S., Wack, S., Aprahamian, M., & Hajri, A. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00506.x · Cited by 89 · see citing works
Sun, C., Yamato, T., Furukawa, T., Ohnishi, Y., Kijima, H., & Horii, A. (2001) · Oncology Reports · doi:10.3892/or.8.1.89 · Cited by 89 · see citing works
Diagnostic utility of K-ras mutations in fine-needle aspirates of pancreatic masses
Villanueva, A., Reyes, G., Cuatrecasas, M., Martinez, A., Erill, N., Lerma, E., Farré, A., Lluı́s, F., & Capellá, G. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8613066 · Cited by 62 · see citing works
Molecular biology of pancreatic cancer
Belda-Iniesta, C., de Cáceres, I. I., Barriuso, J., de Castro, J., Barón, M. G., & Feliú, J. (2008) · Clinical & Translational Oncology · doi:10.1007/s12094-008-0247-6 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer
Kamerkar, S., LeBleu, V. S., Sugimoto, H., Yang, S., Ruivo, C. F., Melo, S. A., Lee, J. J., & Kalluri, R. (2017) · Nature · doi:10.1038/nature22341 · Cited by 2,639 · see citing works
Noncoding RNA therapeutics—Challenges and potential solutions
Winkle, M., El-Daly, S. M., Fabbri, M., & Calin, G. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00219-z · Cited by 1,551 · see citing works
Therapeutic siRNA: state of the art
Hu, B., Zhong, L., Weng, Y., Peng, L., Huang, Y., Zhao, Y., & Liang, X.-J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0207-x · Cited by 1,586 · see citing works
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 · see citing works
Crooke, S. T., Witztum, J. L., Bennett, C. F., & Baker, B. F. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.004 · Cited by 841 · see citing works
Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer
Buscail, L., Bournet, B., & Cordelier, P. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0245-4 · Cited by 721 · see citing works
Advances in the delivery of RNA therapeutics: from concept to clinical reality
Kaczmarek, J. C., Kowalski, P. S., & Anderson, D. G. (2017) · Genome Medicine · doi:10.1186/s13073-017-0450-0 · Cited by 656 · see citing works
siRNA: Mechanism of action, challenges, and therapeutic approaches
Alshaer, W., Zureigat, H., Alkaraki, A., Al-Kadash, A., Gharaibeh, L. F., Hatmal, M. M., Aljabali, A. A. A., & Awidi, A. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174178 · Cited by 450 · see citing works
Clinical experiences with systemically administered siRNA-based therapeutics in cancer
Zuckerman, J. E., & Davis, M. E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4685 · Cited by 424 · see citing works
RNAi-based therapeutics and tumor targeted delivery in cancer
Kara, G., Călin, G. A., & Özpolat, B. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114113 · Cited by 417 · see citing works
RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges
Yu, A., Choi, Y. H., & Tu, M. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019554 · Cited by 405 · see citing works
Therapeutic siRNA: State-of-the-Art and Future Perspectives
Friedrich, M., & Aigner, A. M. (2022) · BioDrugs · doi:10.1007/s40259-022-00549-3 · Cited by 413 · see citing works
Pancreatic Cancer: A Review of Current Treatment and Novel Therapies
Kolbeinsson, H. M., Chandana, S. R., Wright, G. P., & Chung, M. H. (2022) · Journal of Investigative Surgery · doi:10.1080/08941939.2022.2129884 · Cited by 420 · see citing works
Caster, J. M., Patel, A. N., Zhang, T., & Wang, A. Z. (2016) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1416 · Cited by 378 · see citing works
Nucleic acid delivery for therapeutic applications
Gupta, A., Andresen, J. L., Manan, R. S., & Langer, R. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113834 · Cited by 339 · see citing works
Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants
Hofmann, M. H., Gerlach, D., Misale, S., Petronczki, M., & Kraut, N. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1331 · Cited by 336 · see citing works
Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma
Qian, Y., Gong, Y., Fan, Z., Luo, G., Huang, Q., Deng, S., Cheng, H., Jin, K., Ni, Q., Yu, X., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00958-3 · Cited by 312 · see citing works
siRNA therapeutics: a clinical reality
Saw, P. E., & Song, E. (2019) · Science China Life Sciences · doi:10.1007/s11427-018-9438-y · Cited by 292 · see citing works
RNAi therapeutic and its innovative biotechnological evolution
Weng, Y., Xiao, H., Zhang, J., Liang, X., & Huang, Y. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.04.012 · Cited by 288 · see citing works
KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 Mutations in Pancreatic Cancer
Cicenas, J., Kvederavičiūtė, K., Meskinyte, I., Meškinytė-Kaušilienė, E., Skeberdytė, A., & Cicenas, J. (2017) · Cancers · doi:10.3390/cancers9050042 · Cited by 273 · see citing works
Noncoding RNAs in cancer therapy resistance and targeted drug development
Wang, W., Han, C., Sun, Y., Chen, T.-Q., & Chen, Y. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0748-z · Cited by 266 · see citing works
Pharmapolymers in the 21st century: Synthetic polymers in drug delivery applications
Englert, C., Brendel, J. C., Majdanski, T. C., Yildirim, T., Schubert, S., Gottschaldt, M., Windhab, N., & Schubert, U. S. (2018) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2018.07.005 · Cited by 248 · see citing works
Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer
Adiseshaiah, P. P., Crist, R. M., Hook, S. S., & McNeil, S. E. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.119 · Cited by 239 · see citing works
Emerging strategies to target RAS signaling in human cancer therapy
Chen, K., Zhang, Y., Qian, L. M., & Wang, P. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01127-w · Cited by 231 · see citing works
Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach
Chalbatani, G. M., Dana, H., Gharagouzloo, E., Grijalvo, S., Eritja, R., Logsdon, C. D., Memari, F., Miri, S. R., Rad, M. R., & Marmari, V. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s200253 · Cited by 238 · see citing works
Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Zhu, C., Guan, X., Zhang, X., Luan, X., Song, Z., Cheng, X., Zhang, W., & Qin, J.-J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01629-2 · Cited by 231 · see citing works
Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy
Mainini, F., & Eccles, M. R. (2020) · Molecules · doi:10.3390/molecules25112692 · Cited by 225 · see citing works
Biopolymers for Antitumor Implantable Drug Delivery Systems: Recent Advances and Future Outlook
Talebian, S., Foroughi, J., Wade, S. J., Vine, K. L., Dolatshahi‐Pirouz, A., Mehrali, M., Conde, J., & Wallace, G. G. (2018) · Advanced Materials · doi:10.1002/adma.201706665 · Cited by 222 · see citing works
KRAS inhibitors: resistance drivers and combinatorial strategies
Isermann, T., Sers, C., Der, C. J., & Papke, B. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.11.009 · Cited by 207 · see citing works
The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market
Titze‐de‐Almeida, R., David, C., & Titze-de-Almeida, S. S. (2017) · Pharmaceutical Research · doi:10.1007/s11095-017-2134-2 · Cited by 198 · see citing works
Recent Advances in Oligonucleotide Therapeutics in Oncology
Xiong, H., Veedu, R. N., & Diermeier, S. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073295 · Cited by 187 · see citing works
Loganathan, T., & Doss, C. G. P. (2023) · Functional & Integrative Genomics · doi:10.1007/s10142-022-00947-4 · Cited by 190 · see citing works
Efficient nanocarriers of siRNA therapeutics for cancer treatment
Subhan, M. A., & Torchilin, V. P. (2019) · Translational research · doi:10.1016/j.trsl.2019.07.006 · Cited by 182 · see citing works
KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment
Zeitouni, D., Pylayeva‐Gupta, Y., Der, C. J., & Bryant, K. L. (2016) · Cancers · doi:10.3390/cancers8040045 · Cited by 179 · see citing works
Zhang, J., Chen, B., Gan, C., Sun, H., Zhang, J., & Feng, L. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s436038 · Cited by 186 · see citing works
Journey of siRNA: Clinical Developments and Targeted Delivery
Nikam, R. R., & Gore, K. R. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2017.0715 · Cited by 175 · see citing works
Current Advances in RNA Therapeutics for Human Diseases
Zogg, H., Singh, R., & Ro, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052736 · Cited by 173 · see citing works
Tan, D. S.-W., Chong, F. T., Leong, H. S., Toh, S. Y., Lau, D. P., Kwang, X. L., Zhang, X., Sundaram, G. M., Tan, G. S., Chang, M. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4401 · Cited by 164 · see citing works
RNA therapy: Are we using the right molecules?
Yu, A., Jian, C., Yu, A. H., & Tu, M. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.11.011 · Cited by 162 · see citing works
Liu, M., Wang, Y., Zhang, Y.-B., Hu, D., Tang, L., Zhou, B., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02112-8 · Cited by 174 · see citing works
Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy
Chen, C., Yang, Z., & Tang, X. (2018) · Medicinal Research Reviews · doi:10.1002/med.21479 · Cited by 160 · see citing works
Clinical advances of siRNA therapeutics
Hu, B., Weng, Y., Xia, X., Liang, X., & Huang, Y. (2019) · The Journal of Gene Medicine · doi:10.1002/jgm.3097 · Cited by 157 · see citing works
New Treatment Strategies for Metastatic Pancreatic Ductal Adenocarcinoma
Singh, R., & O'Reilly, E. M. (2020) · Drugs · doi:10.1007/s40265-020-01304-0 · Cited by 156 · see citing works
RNA-targeted therapeutics in cancer clinical trials: Current status and future directions
Barata, P. C., Sood, A. K., & Hong, D. S. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.08.004 · Cited by 153 · see citing works
Clinical Advances of siRNA-Based Nanotherapeutics for Cancer Treatment
Hattab, D., Gazzali, A. M., & Bakhtiar, A. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13071009 · Cited by 150 · see citing works
Engineering functional inorganic–organic hybrid systems: advances in siRNA therapeutics
Shen, J., Zhang, W., Qi, R., Mao, Z., & Shen, H. (2018) · Chemical Society Reviews · doi:10.1039/c7cs00479f · Cited by 148 · see citing works
Engineering Nanoparticles for Targeted Delivery of Nucleic Acid Therapeutics in Tumor
Xiao, Y., Shi, K. Y., Qu, Y., Chu, B., & Qian, Z. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.09.002 · Cited by 142 · see citing works
Zhang, H., Vandesompele, J., Braeckmans, K., Smedt, S. C. D., & Remaut, K. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00194f · Cited by 140 · see citing works
Effective tools for RNA-derived therapeutics: siRNA interference or miRNA mimicry
Wang, P., Zhou, Y., & Richards, M. (2021) · Theranostics · doi:10.7150/thno.62642 · Cited by 123 · see citing works
Transcriptomics and solid tumors: The next frontier in precision cancer medicine
Tsimberidou, A. M., Fountzilas, E., Bleris, L. G., & Kurzrock, R. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.09.007 · Cited by 114 · see citing works
Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer
Stefanoudakis, D., Frountzas, M., Schizas, D., Michalopoulos, N. V., Drakaki, A., & Toutouzas, K. G. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46040177 · Cited by 110 · see citing works
Modulating epigenetic modifications for cancer therapy (Review)
Castro-Muñoz, L. J., Vázquez‐Ulloa, E., Sahlgren, C., Lizano, M., la Cruz-Hernández, E. N. D., & Contreras‐Paredes, A. (2023) · Oncology Reports · doi:10.3892/or.2023.8496 · Cited by 106 · see citing works
Targeted siRNA lipid nanoparticles for the treatment of KRAS-mutant tumors
Anthiya, S., Öztürk, S. C., Yanık, H., Tavukçuoğlu, E., Şahin, A., Datta, D., Charissé, K., Moreira, D., Loza, M. I., Calvo, A., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.03.016 · Cited by 101 · see citing works
Exosome‐mediated small RNA delivery for gene therapy
Zhou, Y., Zhou, G., Tian, C., Jiang, W., Jin, L., Zhang, C., & Chen, X. (2016) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1363 · Cited by 103 · see citing works
Grillone, K., Caridà, G., Luciano, F., Cordua, A., Martino, M. T. D., Tagliaferri, P., & Tassone, P. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05554-4 · Cited by 100 · see citing works
Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC)
Chandana, S. R., Babiker, H. M., & Mahadevan, D. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2019.1557145 · Cited by 98 · see citing works
Transcription and Translation Inhibitors in Cancer Treatment
Laham-Karam, N., Pinto, G., Poso, A., & Kokkonen, P. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.00276 · Cited by 88 · see citing works
López-Estévez, A. M., Lapuhs, P., Pineiro‐Alonso, L., & Alonso, M. J. (2023) · Advanced Materials · doi:10.1002/adma.202309355 · Cited by 90 · see citing works
Kirsten Ras* oncogene: Significance of its discovery in human cancer research
Tsuchida, N., Murugan, A. K., & Grieco, M. (2016) · Oncotarget · doi:10.18632/oncotarget.8773 · Cited by 87 · see citing works
Current status and future perspectives of gold nanoparticle vectors for siRNA delivery
Artiga, Á., Serrano‐Sevilla, I., Matteis, L. D., Mitchell, S. G., & de la Fuente, J. M. (2019) · Journal of Materials Chemistry B · doi:10.1039/c8tb02484g · Cited by 87 · see citing works
Non-Coding RNAs in Cancer Diagnosis and Therapy: Focus on Lung Cancer
Le, P., Romano, G., Nana-Sinkam, P. S., & Acunzo, M. (2021) · Cancers · doi:10.3390/cancers13061372 · Cited by 83 · see citing works
Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges
Tang, D., Kroemer, G., & Kang, R. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01422-7 · Cited by 80 · see citing works
Using Genome Sequence to Enable the Design of Medicines and Chemical Probes
Angelbello, A. J., Chen, J. L., Childs‐Disney, J. L., Zhang, P., Wang, Z.-F., & Disney, M. D. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00504 · Cited by 80 · see citing works
McIntyre, C. A., Lawrence, S., Richards, A. L., Chou, J. F., Wong, W., Capanu, M., Berger, M. F., Donoghue, M. T. A., Yu, K. H., Varghese, A. M., et al. (2020) · Cancer · doi:10.1002/cncr.33038 · Cited by 75 · see citing works
Lipid Nanoparticles for Organ-Specific mRNA Therapeutic Delivery
Żak, M. M., & Zangi, L. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13101675 · Cited by 75 · see citing works
Bahrami, A., Hassanian, S. M., Shahidsales, S., Farjami, Z., Hasanzadeh, M., Anvari, K., Aledavood, A., Maftouh, M., Ferns, G. A., Khazaei, M., et al. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25890 · Cited by 74 · see citing works
Bukhari, S. N. A. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14040866 · Cited by 74 · see citing works
Jonckheere, N., Vasseur, R., & SEUNINGEN, I. V. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.01.002 · Cited by 71 · see citing works
RNA Therapeutics - Research and Clinical Advancements
Feng, R., Patil, S., Zhao, X., Miao, Z., & Qian, A. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.710738 · Cited by 73 · see citing works
Sexton, R. E., Mpilla, G., Kim, S. H., Philip, P. A., & Azmi, A. S. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.02.004 · Cited by 70 · see citing works
Schultheis, B. S., Strumberg, D., Kuhlmann, J. B., Wolf, M., Link, K., Seufferlein, T. T. W., Kaufmann, J., Feist, M., Gebhardt, F., Khan, M., et al. (2020) · Cancers · doi:10.3390/cancers12113130 · Cited by 70 · see citing works
Beyond Lipids: Exploring Advances in Polymeric Gene Delivery in the Lipid Nanoparticles Era
Jogdeo, C. M., Siddhanta, K., Das, A., Ding, L., Panja, S., Kumari, N., & Oupický, D. (2024) · Advanced Materials · doi:10.1002/adma.202404608 · Cited by 72 · see citing works
miRNA and Gene Expression in Pancreatic Ductal Adenocarcinoma
Tesfaye, A. A., Azmi, A. S., & Philip, P. A. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.10.005 · Cited by 70 · see citing works
Huang, J., & Xiao, K. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14081586 · Cited by 72 · see citing works
Treating Cystic Fibrosis with mRNA and CRISPR
Sanchez, A. D. S., Paunovska, K., Cristian, A., & Dahlman, J. E. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.137 · Cited by 72 · see citing works
Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer
Liu, Z., Parveen, N., Rehman, U., Aziz, A., Sheikh, A., Abourehab, M. A. S., Guo, W., Huang, J., Wang, Z., & Kesharwani, P. (2023) · Molecular Cancer · doi:10.1186/s12943-022-01696-5 · Cited by 69 · see citing works
Combinatorial therapeutic approaches with RNAi and anticancer drugs using nanodrug delivery systems
Babu, A., Munshi, A., & Ramesh, R. (2017) · Drug Development and Industrial Pharmacy · doi:10.1080/03639045.2017.1313861 · Cited by 68 · see citing works
Ramot, Y., Rotkopf, S., Gabai, R. M., Zorde Khvalevsky, E., Muravnik, S., Marzoli, G. A., Domb, A. J., Shemi, A., & Nyska, A. (2016) · Toxicologic Pathology · doi:10.1177/0192623316645860 · Cited by 64 · see citing works
Self-citationClinical Applications of Short Non-Coding RNA-Based Therapies in the Era of Precision Medicine
Smith, E. S., Whitty, E., Yoo, B., Moore, A. V., Sempere, L. F., & Medarova, Z. O. (2022) · Cancers · doi:10.3390/cancers14061588 · Cited by 64 · see citing works
Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies
Bazeed, A. Y., Day, C. M., & Garg, S. (2022) · Cancers · doi:10.3390/cancers14174257 · Cited by 65 · see citing works
RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions
MacLeod, A. R., & Crooke, S. T. (2017) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.957 · Cited by 61 · see citing works
Ongoing Clinical Trials of Nonviral siRNA Therapeutics
Narasipura, E. A., VanKeulen‐Miller, R., Ma, Y., & Fenton, O. S. (2023) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.3c00205 · Cited by 63 · see citing works
Biodegradable polymers in gene‐silencing technology
Hosseinkhani, H., & Domb, A. J. (2019) · Polymers for Advanced Technologies · doi:10.1002/pat.4713 · Cited by 58 · see citing works
Self-citationQattan, A. T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238905 · Cited by 58 · see citing works
Targeting the undruggable in pancreatic cancer using nano-based gene silencing drugs
Kokkinos, J., Ignacio, R. M. C., Sharbeen, G., Boyer, C. A., Gonzales‐Aloy, E., Goldstein, D., Initiative, A. P. C. G., McCarroll, J. A., & Phillips, P. A. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2019.119742 · Cited by 57 · see citing works
Shen, H., Lundy, J., Strickland, A. H., Harris, M., Swan, M. P., Desmond, C., Jenkins, B. J., & Croagh, D. G. (2022) · Cells · doi:10.3390/cells11193175 · Cited by 57 · see citing works
KRAS: the Achilles’ heel of pancreas cancer biology
Drizyte‐Miller, K., Talabi, T., Somasundaram, A., Cox, A. D., & Der, C. J. (2025) · Journal of Clinical Investigation · doi:10.1172/jci191939 · Cited by 63 · see citing works
Targeting the undruggable oncogenic KRAS: the dawn of hope
Asimgil, H., Ertetik, U., Çevik, N. C., Ekizce, M., Doğruöz, A., Gökalp, M., Sever, E. A., Istvánffy, R., Friess, H., Ceyhan, G. O., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.153688 · Cited by 55 · see citing works
KRAS: A Druggable Target in Colon Cancer Patients
Negri, F., Bottarelli, L., de’Angelis, G. L., & Gnetti, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084120 · Cited by 55 · see citing works
The Clinical Potential of Oligonucleotide Therapeutics against Pancreatic Cancer
Takakura, K., Kawamura, A., Torisu, Y., Koido, S., Yahagi, N., & Saruta, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133331 · Cited by 54 · see citing works
Bianchi, A. S., Loupakis, F., Argilés, G., & Prager, G. W. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw191 · Cited by 54 · see citing works
Pancreatic Cancer and Its Microenvironment—Recent Advances and Current Controversies
Stopa, K. B., Kusiak, A. A., Szopa, M. D., Ferdek, P. E., & Jakubowska, M. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093218 · Cited by 54 · see citing works
Wang, J., Yang, J., Li, D., & Li, J. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188454 · Cited by 53 · see citing works
The importance of Ras in drug resistance in cancer
Healy, F. M., Prior, I. A., & MacEwan, D. J. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15420 · Cited by 52 · see citing works
Noncoding RNAs in Glioblastoma: Emerging Biological Concepts and Potential Therapeutic Implications
Shahzad, U., Krumholtz, S. L., Rutka, J. T., & Das, S. (2021) · Cancers · doi:10.3390/cancers13071555 · Cited by 49 · see citing works
Roostaee, M., Derakhshani, A., Mirhosseini, H., Mofakham, E. B., Fathi‐karkan, S., Mirinejad, S., Sargazi, S., & Barani, M. (2023) · Nanoscale · doi:10.1039/d3nr03495j · Cited by 49 · see citing works
Targeting KRAS mutations in pancreatic cancer: opportunities for future strategies
Linehan, A., O’Reilly, M., McDermott, R., & O'Kane, G. M. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1369136 · Cited by 50 · see citing works
Disulfide Bridging Strategies in Viral and Nonviral Platforms for Nucleic Acid Delivery
Dutta, K., Das, R., Medeiros, J., & Thayumanavan, S. (2021) · Biochemistry · doi:10.1021/acs.biochem.0c00860 · Cited by 48 · see citing works
Barresi, V., Musmeci, C., Rinaldi, A., & Condorelli, D. F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23168875 · Cited by 47 · see citing works
Targeting KRAS in Solid Tumors: Current Challenges and Future Opportunities of Novel KRAS Inhibitors
Indini, A., Rijavec, E., Ghidini, M., Cortellini, A., & Grossi, F. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050653 · Cited by 47 · see citing works
- Authors
- Golan, T., Khvalevsky, E. Z., Hubert, A., Gabai, R. M., Hen, N., Segal, A., Domb, A., Harari, G., David, E. B., Raskin, S., Goldes, Y., Goldin, E., Eliakim, R., Lahav, M., Kopleman, Y., Dancour, A., Shemi, A., & Galun, E.
- Affiliations
- Tel Aviv University (IL)
- Silenseed Ltd., Jerusalem, Israel
- Hadassah Medical Center (IL)
- Shaare Zedek Medical Center (IL)
- Hebrew University of Jerusalem (IL)
- MediStat Ltd., Jerusalem, Israel
- Hadassah-Hebrew University Medical Centre, Jerusalem, Israel
- ORCID
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2015-05-19
- Volume
- 6
- Issue
- 27
- Pages
- 24560-24570
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4695206
- OpenAlex
- W1780086376
- Cited by
- 336
- References
- 21
- Citations by year
- 2026: 27 · 2025: 27 · 2024: 39 · 2023: 36 · 2022: 39 · 2021: 39 · 2020: 30 · 2019: 20 · 2018: 32 · 2017: 26 · 2016: 16 · 2015: 5
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- KRAS, pancreatic cancer, siRNA, RNAi therapy, KRAS G12D, biodegradable polymer implants, local drug delivery, combination chemotherapy, locally advanced pancreatic cancer, first-line therapy, overall survival, targeted therapy, siRNA toxicity
- MeSH terms
- RNAi Therapeutics, Irinotecan, Oxaliplatin, Gemcitabine, Aged, Aged, 80 and over, Antigens, Neoplasm, Antineoplastic Agents, Camptothecin, Leucovorin, Combined Modality Therapy, Deoxycytidine, Drug Implants, Female, Fluorouracil, Humans, Male, Middle Aged, Organoplatinum Compounds, Pancreatic Neoplasms, Proto-Oncogene Proteins p21(ras), Disease-Free Survival, Absorbable Implants, Carcinoma, Pancreatic Ductal, RNA, Small Interfering, Molecular Targeted Therapy
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