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Novel cancer treatment using nucleic acid medicine Nek2 siRNA

  • School of Medicine/Graduate School of Medicine
  • Program in function Construction Medicine
  • Surgery
  • Surgical Oncology

Toshio Kokuryo [Assistant Professor]

http://www.med.nagoya-u.ac.jp/english01/6489/6582/Surgical-Oncology.html

Outline of Seeds

Cancer is the first-leading cause of deaths in Japan. Despite developments of various treatments for cancer, the clinical outcome has not been markedly improved. Novel strategies are required to treat pancreatic cancer, especially for local recurrence, peritoneal dissemination and liver metastases. Nucleic acid medicine is thought to be a next-generation medicine. siRNA (short interfering RNA) is one of nucleic acid medicine, such as Aptamer and microRNA. We developed the molecular target therapy using siRNA targeted Nek2 (NIMA related kinase 2).

Novelty and originality of this research

Nek2 is a member of the serine/threonine kinase family, related to the essential mitotic regulator NIMA. Nek2 is involved in cell division and mitotic regulation by centrosome splitting. We reported that Nek2 siRNA suppressed the tumor growth in xenograft cancer model. In peritoneal dissemination model, Nek2 siRNA-treated mice showed statistically significant longer survival periods in comparison with those of the control siRNA-treated mice. We started a translational research entitled "Analysis of novel treatment using Nek2 siRNA for non-curative pancreas cancer" from June 2013. This world first treatment was developed by Nagoya University.

Application and research area for Industry collaboration

To evaluate the safety and efficacy for local injection of Nek2 siRNA with three different doses, we started the translational research, entitled "Analysis of novel treatment using Nek2 siRNA for non-curative pancreas cancer".
Eligibility Criteria: 1) Subjects who are histologically, cytologically and/or clinically diagnosed having a pancreas cancer, and are going to undergo palliative operation, such as gastrojejunostomy and choledochojejunostomy. 2) Anticancer therapies, such as chemotherapy and radiotherapy are no longer effective, or are unlikely to be effective. 3) Age ≥ 18 years, ≤ 70 years. 4) ECOG performance score is 0-2. 5) Life expectancy is at least 3 months. 6) Subjects must have at least one measurable lesion, such as maximum length ≥ 10mm and maximum tumor volume ≤ 25.2 cm3.
Primary outcomes are safety and tolerability, and secondary outcome is anticancer effect.
Results: Nek2 siRNA efficiently prevented the progression of pancreas cancer. There were no adverse side effects related to Nek2 siRNA. We are developing novel strategies to treat various cancers, especially for peritoneal dissemination and liver metastases.

Key Takeaway

Novel treatments for malignancies are urgent and important issues. Nek2 siRNA demonstrated anti-cancer effect and no adverse side effects in the first-in-human trial. Nek2 is considered to be an effective target for the treatment of cancers. Further investigation is required for early clinical application of Nek2 siRNA to improve the prognosis of cancer patients.

Keywords

Nucleic acid medicine, Nek2, siRNA, Cancer treatment

Technologies

  • Technology for the administration of siRNA
  • Technology for the formulation of siRNA-complex using biocollagen

Patents

  • Oligonucleotide inhibiting tumor cell proliferation and method therefor, PCT/JP2005/011227

Monographs, Papers and Articles

  • Kokuryo T, Senga T, Yokoyama Y, Nagino M, Nimura Y, Hamaguchi M.: Nek2 as an effective target for inhibition of tumorigenic growth and peritoneal dissemination of cholangiocarcinoma. Cancer Res. 67(20):9637-42.2007
  • Tsunoda N, Kokuryo T, Oda K, Senga T, Yokoyama Y, Nagino M, Nimura Y, Hamaguchi M.: Nek2 as a novel molecular target for the treatment of breast carcinoma. Cancer Sci. 100(1):111-6. 2009
  • Suzuki K, Kokuryo T, Senga T, Yokoyama Y, Nagino M, Hamaguchi M.: Novel combination treatment for colorectal cancer using Nek2 siRNA and cisplatin. Cancer Sci. 101(5):1163-9. 2010
  • Kokuryo T, Hibino S, Suzuki K, Watanabe K, Yokoyama Y, Nagino M, Senga T, Hamaguchi M. : Nek2 siRNA therapy using a portal venous port-catheter system for liver metastasis in pancreatic cancer. Cancer Sci. 107(9):1315-20. 2016