Clinical experiences with systemically administered siRNA-based therapeutics in cancer

Nature Reviews Drug Discovery

Volumn 14, Issue 12, 2015, Pages 843-856

  Zuckerman, Jonathan E ^a   Davis, Mark E ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b California Institute of Technology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALN VSP; ANTINEOPLASTIC AGENT; ATU 027; CALAA 01; DCR MYC; GEMCITABINE; LIPID; MRX 34; NAKED SMALL INTERFERING RNA; NANOPARTICLE; PATISIRAN; PNT 2258; POLYETHYLENEIMINE; POLYMER; REVUSIRAN; SIG12D LODER; SINGLE STRANDED DNA; SMALL INTERFERING RNA; SMALL INTERFERING RNA EPHRIN TYPE A RECEPTOR 2 1,2 DIOLELOYL SN GLYCERO 3 PHOSPHATIDYLCHOLINE; SNS01 T; TKM PLK1; UNCLASSIFIED DRUG;

ASTHENIA; BACKACHE; CANCER GENE THERAPY; CHILL; DIARRHEA; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG EFFICACY; DRUG FORMULATION; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TARGETING; DRUG TOLERANCE; FATIGUE; FEVER; GENE; GENE DELIVERY SYSTEM; HEADACHE; HUMAN; INFUSION RELATED REACTION; NAUSEA; NAUSEA AND VOMITING; NONHUMAN; ONCOGENE K RAS; PANCREAS ADENOCARCINOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PIK3CA GENE; PIK3CB GENE; PRIORITY JOURNAL; REVIEW; RIGOR; RNA INTERFERENCE; SOLID TUMOR; SPLENOMEGALY; TASTE DISORDER; VOMITING; GENE SILENCING; NEOPLASMS; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS, PHASE I AS TOPIC; GENE SILENCING; HUMANS; NEOPLASMS; RNA, SMALL INTERFERING; TREATMENT OUTCOME;

EID: 84948717926     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd4685     Document Type: Review

References (91)

1. Fire, A. Z. Gene silencing by double-stranded RNA (Nobel Lecture). Angew. Chem. Int. Ed. 46, 6966-6984 (2007
2. Burnett, J. C.,&Rossi, J. J. RNA-based therapeutics: current progress and future prospects. Chem. Biol. 19, 60-71 (2012
3. Vaishnaw, A. K., et al A status report on RNAi therapeutics. Silence 1, 14 (2010
4. de Fougerolles, A., Vornlocher, H. P., Maraganore, J.,&Lieberman, J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov. 6, 443-453 (2007
5. Sepp-Lorenzino, L.,&Ruddy, M. K. Challenges and opportunities for local and systemic delivery of siRNA and antisense oligonucleotides. Clin. Pharmacol. Ther. 84, 628-632 (2008
6. Whitehead, K. A., Langer, R.,&Anderson, D. G. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8, 129-138 (2009
7. Chen, S. H.,&Zhaori, G. Potential clinical applications of siRNA technique: benefits and limitations. Eur. J. Clin. Invest. 41, 221-232 (2011
8. Pecot, C. V., Calin, G. A., Coleman, R. L., Lopez-Berestein, G.,&Sood, A. K. RNA interference in the clinic: challenges and future directions. Nat. Rev. Cancer 11, 59-67 (2011
9. Wu, S. Y., Lopez-Berestein, G., Calin, G. A.,&Sood, A. K. RNAi therapies: drugging the undruggable. Sci. Transl. Med. 6, 240ps7 (2014
10. Davis, M. E., Chen, Z. G.,&Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7, 771-782 (2008
11. Egusquiaguirre, S. P., Igartua, M. Hernández, R. M.,&Pedraz, J. L. Nanoparticle delivery systems for cancer therapy: advances in clinical and preclinical research. Clin. Transl. Oncol. 14, 83-93 (2012
12. Kanasty, R., Dorkin, J. R., Vegas, A.,&Anderson, D. Delivery materials for siRNA therapeutics. Nat. Mater. 12, 967-977 (2013
13. Gomes da Silva, L. C., Simões, S.,&Moreira, J. N. Challenging the future of siRNA therapeutics against cancer: the crucial role of nanotechnology. Cell. Mol. Life Sci. 21, 1417-1438 (2014
14. Behlke, M. A. Chemical modification of siRNAs for in vivo use. Oligonucleotides 18, 305-320 (2008
15. Rettig, G. R.,&Behlke, M. A. Progress toward in vivo use of siRNAs-II. Mol. Ther. 20, 483-512 (2012
16. Bartlett, D. W.,&Davis, M. E. Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-Animal bioluminescent imaging. Nucl. Acids Res. 34, 322-333 (2006
17. Bartlett, D. W.,&Davis, M. E. Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticles. Biotech. Bioeng. 99, 975-985 (2008
18. Yuan, T. L., et al. Development of siRNA payloads to target KRAS-mutant cancer. Cancer Discov. 4, 1182-1197 (2014
19. Koldehoff, M., Steckel, N. K., Beelen, D. W.,&Elmaagacli, A. H. Therapeutic application of small interfering RNA directed against BCR-ABL transcripts to a patient with imatinib-resistant chronic myeloid leukaemia. Clin. Exp. Med. 7, 47-55 (2007
20. Molitoris, B. A., et al. siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J. Am. Soc. Nephrol. 20, 1754-1764 (2009
21. Petros, R. A.,&DeSimone, J. M. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9, 615-627 (2010
22. Coelho, T., et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N. Engl. J. Med. 369, 819-829 (2013
23. Fitzgerald, K., et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blinded placebo-controlled, Phase 1 trial. Lancet 383, 60-68 (2014
24. Nair, J. K., et al. Multivalent N-Acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J. Am. Chem. Soc. 136, 16958-16961 (2014
25. Golan, T., et al. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients. Oncotarget [online], http://www.impactjournals.com/oncotarget/index.php?. journal=oncotarget&page=article&op=view&path% 5B%5D=4183&path%5B%5D=9307 (2015
26. Farooqi, A. A., Rehman, Z.,&Muntane, J. Antisense therapeutics in oncology: current status. Onco. Targets Ther. 7, 2035-2042 (2014
27. Davis, M. E., et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464, 1067-1070 (2010
28. Zuckerman, J. E., et al. Correlating animal and human Phase Ia/Ib clinical data with CALAA 01, a targeted, polymer-based nanoparticle containing siRNA. Proc. Natl Acad. Sci. USA 111, 11449-11454 (2014
29. Tabernero, J., et al. First in humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov. 3, 406-417 (2013
30. Strumberg, D., et al. Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors. Int. J. Clin. Pharm. Ther. 50, 76-78 (2012
31. Schultheis, B., et al. First in human Phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors. J. Clin. Oncol. 32, 4141-4148 (2014
32. Ramanathan, R. K., et al A Phase 1 dose escalation study of TKM 080301, a RNAi therapetuic directed against PLK1, in patients with advanced solid tumors. J. Clin. Oncol. 31 (Suppl), TPS2621 (2013
33. Tolcher, A. W., et al A Phase 1 study of the BCL2 targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors. Cancer Chemoth. Pharm. 73, 363-371 (2014
34. Davis, M. E. The first targeted delivery of siRNA in humans via a self-Assembling cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol. Pharm. 6, 659-668 (2009
35. Davis, M. E. Fighting cancer with nanoparticle medicines - the nanoscale matters. MRS Bull. 37, 828-835 (2012
36. Grimm, D., et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441, 537-541 (2006
37. Heidel, J. D., et al. Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin. Cancer Res. 13, 2207-2215 (2007
38. Barros, S. A.,&Gollob, J. A. Safety profile of RNAi nanomedicines. Adv. Drug Deliv. Rev. 64, 1730-1737 (2012
39. Judge, A. D., et al. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice. J. Clin. Invest. 119, 661-673 (2009
40. Sioud, M. Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: a central role for 2? hydroxyl uredines in immune responses. Eur. J. Immunol. 36, 1222-1230 (2006
41. Heidel, J. D., et al. Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase submit M2 siRNA. Proc. Natl Acad. Sci. USA 104, 5715-5721 (2007
42. Inaba, S., et al. Atelocollagen-mediated systemic delivery prevents immunostimulatory adverse effects of siRNA in mammals. Mol. Ther. 20, 356-366 (2012
43. Moyano, D. F., et al. Nanoparticle hydrophobicity dictates immune response. J. Am. Chem. Soc. 134, 3965-3967 (2012
44. Hickerson, R. P., et al. Stability study of unmodified siRNA and relevance to clinical use. Oligonucleotides 18, 1-10 (2008
45. Bartlett, D. W.,&Davis, M. E. Effect of siRNA nuclease stability on the in vitro and in vivo kinetics of siRNA-mediated gene silencing. Biotechnol. Bioeng. 97, 909-921 (2007
46. Zuckerman, J. E., Hsueh, T., Koya, R. C., Davis, M. E.,&Ribas, A. siRNA knockdown of ribonucleotide reductase inhibits melanoma cell line proliferation alone or synergistically with temozolomide. J. Invest. Derm. 131, 453-460 (2011
47. Cheng, Z., et al. Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science 338, 903-910 (2012
48. Hu Lieskovan, S., Heidel, J. D., Bartlett, D. W., Davis, M. E.,&Triche, T. J. Sequence-specific knockdown of EWS FL1 by targeted, nonviral delivery of small interfering, RNA inhibits tumor growth in a murine model of metastatic Ewings sarcoma. Cancer Res. 65, 8984-8992 (2005
49. Bartlett, D. W., Su, H., Hildebrandt, I. J., Weber, W. A.,&Davis, M. E. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl Acad. Sci. USA 104, 15549-15554 (2007
50. Sykes, E. A., et al. Investigating the impact of nanoparticle size on active and passive tumor targeting efficiency. ACS Nano. 8, 5696-5706 (2014
51. Senzer, N., et al. Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors. Mol. Ther. 21, 1096-1103 (2013
52. Bertrand, N., et al. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv. Drug Del. Rev. 66, 2-25 (2014
53. Zuckerman, J. E., Choi, C. H. J., Han, H.,&Davis, M. E. Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane. Proc. Natl Acad. Sci. USA 109, 3137-3142 (2012
54. Naeye, B., et al. In vivo disassembly of IV administered siRNA matrix nanoparticles at the renal filtration barrier. Biomaterials 34, 2350-2358 (2013
55. Song, G., Wu, H., Yoshino, K.,&Zamboni, W. C. Factors affecting the pharmacokinetics and pharmacodynamics of liposomal drugs. J. Liposome Res. 22, 177-192 (2012
56. Eliasof, S., et al. Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle. Proc. Natl Acad. Sci. USA 110, 15127-15132 (2013
57. Stein, C. A.,&Goel, S. Therapeutic oligonucleotides: the road not taken. Clin. Cancer Res. 17, 6369-6372 (2011
58. No authors listed.] Time to deliver. Nat. Biotech. 32, 961 (2014
59. Merritt, W. M., Bar-Eli, M.,&Sood, A. K. The dicey role of Dicer: implications for RNAi therapy. Cancer Res. 70, 2571-2574 (2010
60. Merritt, W. M., et al. Dicer, drosha, and outcomes in patients with ovarian cancer. N. Engl. J. Med. 359, 2641-2650 (2008
61. Caffrey, E., et al. Prognostic significance of deregulated dicer expression in breast cancer. PLoS ONE 8, e83724 (2013
62. Daige, C. L., et al. Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer. Mol. Cancer Ther. 13, 2352-2360 (2014
63. Cheng, C. J., et al. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 518, 107-110 (2015
64. Pennisi, E. The CRISPR craze. Science 341, 833-836 (2013
65. Dounda, J A.,&Charpenter, E the New Frontier of Genome Engineering with CRISPER Cas9. Science 346, 1258096 (2014
66. Tang, L., et al. Investigating the optimal size of anticancer nanomedicine. Proc. Natl Acad. Sci. USA 111, 15344-15349 (2014
67. Adjei, I. M., et al. Heterogeneity in nanoparticles influences biodistribution and targeting. Nanomedicine 9, 267-278 (2014
68. Zhang, J., et al. Assessing the heterogeneity level in lipid nanoparticles for siRNA delivery: size-based separation, compositional heterogeneity, and impact on bioperformance. Mol. Pharm. 10, 397-405 (2013
69. Maier, M. A., et al. Biodegradable lipids enabling rapidly eliminated lipid nanoparticle for systemic delivery of RNAi therapeutics. Mol. Ther. 21, 1570-1578 (2013
70. Whitehead, K. A., et al. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat. Commun. 5, 4277 (2014
71. Barrett, S. E., et al. Development of a liver-Targeted siRNA delivery platform with a broad therapeutic window utilizing biodegradable polypeptide-based polymer conjugates. J. Control. Release 183, 124-137 (2014
72. Lane, L. A., Qian, X., Smith, A. M.,&Nie, S. Physical chemistry of nanomedicine: understanding the complex behavior of nanoparticles in vivo. Annu. Rev. Phys. Chem. 66, 521-547 (2015
73. Landesman-Milo, D.,&Peer, D. Toxicity profiling of several common RNAi-based nanomedicines: a comparative study. Drug Deliv. Transl. Res. 4, 96-103 (2014
74. Hwang, T., Aljuffali, I. A., Lin, C., Chang, Y.,&Fang, J. Cationic additives in nanosystems activate cytotoxicity and imflammatory response of human neutrophils: lipid nanoparticles versus polymeric nanoparticles. Int. J. Nanomed. 10, 371-385 (2015
75. Robbins, G. R., et al. Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model. Nanomedicine 11, 589-599 (2015
76. Li, L., et al. Tumor vasculature is a key determinant of the efficiency of nanoparticle-mediated siRNA delivery. Gene Ther. 19, 775-780 (2012
77. Cabral, H., et al. Accumulation of sub 100nm polymeric micelles in poorly permeable tumours depends on size. Nat. Nanotech. 6, 815-823 (2011
78. Prabhaker, U., et al. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res. 73, 2412-2417 (2013
79. Koukourakis, M. I., et al. Liposomal doxorubicin and conventionally fractionated radiotherapy in the treatment of locally advanced non-small-cell lung cancer and head and neck cancer. J. Clin. Oncol. 17, 3512-3521 (1999
80. Karrington, K. J., et al. Effective targeting of solid tumors in patients with locally advanced cancer by radiolabeled pegylated liposomes. Clin. Cancer Res. 7, 243-254 (2001
81. Cuellar, T. L., et al. Systemic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB-siRNA conjugates. Nucleic Acids Res. 43, 1189-1203 (2015
82. Weiss, G. J., et al. First in human Phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies. Invest. New Drugs 31, 986-1000 (2013
83. Suetsugu, A., et al. Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models. Adv. Drug Del. Rev. 65, 383-390 (2013
84. Sehgal, A. Chen, Q. Gibbings, D., Sah, D. W. Y.,&Bumcrot, D. Tissue-specific gene silencing monitored in circulating RNA. RNA 20, 1-7 (2014
85. Antanaviciute, I., et al. Long-distance communication between laryngeal carcinoma cells. PLoS ONE 9, e99196 (2014
86. Melo, S. A., et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26, 707-721 (2014
87. Hannafon, B. N.,&Ding, W. Intercellular comminucaiton by exosome-derived microRNAs in cancer. Int. J. Mol. Sci. 14, 14240-14269 (2013
88. Roberts, C. T. Jr&Kurre, P. Vesicle trafficking and RNA transfer add complexity and connectivity to cell-cell communication. Cancer Res. 73, 3200-3205 (2015
89. Dienstmann, R., et al. Safety and activity of the first in class Sym004 anti-EGFR antibody mixture in patients with refractory colorectal cancer. Cancer Discov. 5, 598-609 (2015
90. Sharma, S. V., Bell, D. W., Settleman, J.,&Haber, D. A. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7, 169-181 (2007
91. Fedornko, I. V., Gibney, G. T., Sondak, V. K.,&Smalley, K. S. M. Beyond, BRAF: where next for melanoma therapy?. Br. J. Cancer 112, 217-226 (2015