新型纳米药物抑制小鼠胰腺癌的进展

诸平

据以色列特拉维夫大学（Tel Aviv University, TAU）2018年1月2日提供的消息，该大学的研究人员与以色列希伯来大学（The Hebrew University）、以色列的希巴医疗中心（Sheba Medical Center）以及美国马里兰大学（University of Maryland）的研究人员合作完成了一项新研究：发现新型纳米药物可以抑制小鼠胰腺癌的进展。

这项研究成果已经在《自然通讯》（Nature Communications）杂志网站2018年1月2日发表——Hadas Gibori, Shay Eliyahu, Adva Krivitsky, Dikla Ben-Shushan, Yana Epshtein, Galia Tiram, Rachel Blau, Paula Ofek, Joo Sang Lee, Eytan Ruppin, Limor Landsman, Iris Barshack, Talia Golan, Emmanuelle Merquiol, Galia Blum, RonitSatchi-Fainaro. Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer. Nature Communications, 2018, 9, Article number: 16. doi:10.1038/s41467-017-02283-9. Published online: 02 January 2018. s41467-017-02283-9.pdf

此项成果是由TAU萨克医学院(Sackler Faculty of Medicine) 生理学和药理学系主任Ronit Satchi-Fainaro教授领导的研究小组完成的。参与此项研究的还有Hadas Gibori和Shay Eliyahu博士（Dr. Shay Eliyahu）,他们都是Ronit Satchi-Fainaro教授多学科实验室的研究人员；与Ronit Satchi-Fainaro教授合作的还有TAU计算机科学学院（Blavatnik School of ComputerSciences）的Eytan Ruppin教授（Prof. Eytan Ruppin），Eytan Ruppin教授也在美国马里兰大学计算机科学系与生物信息学及计算生物学中心（Department of ComputerScience and Center for Bioinformatics and Computational Biology, University ofMaryland）任职，也有马里兰大学的其他人员参与。以色列希巴医疗中心（Sheba Medical Center）等研究人员参加。

文章指出一种已知的致癌基因,也就是一种促进癌症发展的基因和一种致癌抑制基因microRNA（oncosuppressor microRNA）的表达之间的博弈，是延长胰腺癌患者得以存活的原因所在，这可能是为胰腺癌这种致命疾病和其他癌症研制有效的鸡尾酒疗法的基础。因为，胰腺癌是目前已知的最具侵袭性的癌症之一。绝大多数的胰腺癌患者在确诊一年后就会死亡。Satchi-Fainaro教授（Prof. Satchi-Fainaro）说：“尽管现代医学提供了所有的治疗手段，但75%的胰腺癌患者在确诊后的12个月内死亡，其中包括许多在短短几个月内死亡的患者。但在被诊断出的患者中，约有7%的人能存活超过5年。我们试图检查那些幸存者和其他病人的区别。我们认为，如果我们能理解为什么一些胰腺癌患者，是如何与这种最具侵略性的疾病抗衡而生活几年的，我们也许就能制定出一种新的治疗策略。”更多信息请注意浏览：

Novel nanomedicine inhibits progression of pancreatic cancer in mice

January 2, 2018, Tel Aviv University

Credit: CC0 Public Domain

A new Tel Aviv University study pinpoints the inverse correlation between a known oncogene—a gene that promotes the development of cancer—and the expression of an oncosuppressor microRNA as the reason for extended pancreatic cancer survival. The study may serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers.

Thestudy, which was published in Nature Communications, was led by Prof.Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology atTAU's Sackler Faculty of Medicine, and conducted by Hadas Gibori and Dr. ShayEliyahu, both of Prof. Satchi-Fainaro's multidisciplinary laboratory, incollaboration with Prof. Eytan Ruppin of TAU's Computer Science Department andthe University of Maryland and Prof. Iris Barshack and Dr. Talia Golan of ChaimSheba Medical Center, Tel Hashomer.

Pancreatic cancer is among the mostaggressive cancers known today. The overwhelming majority of pancreatic cancerpatients die within just a year of diagnosis. "Despite all the treatmentsafforded by modern medicine, some 75% of all pancreatic cancer patients diewithin 12 months of diagnosis, including many who die within just a fewmonths," Prof. Satchi-Fainaro says.

"Butaround seven percent of those diagnosed will survive more than five years. Wesought to examine what distinguishes the survivors from the rest of thepatients," Prof. Satchi-Fainaro continues. "We thought that if wecould understand how some people live several years with this most aggressivedisease, we might be able to develop a new therapeutic strategy."

Callinga nano-taxi

Theresearch team examined pancreatic cancer cells and discovered an inversecorrelation between the signatures of miR-34a, a tumor suppressant, andPLK1, a known oncogene. The levels of miR-34a were low in pancreatic cancermouse models, while the levels of the oncogene were high. This correlation madesense for such an aggressive cancer. But the team needed to see if the same wastrue in humans.

Thescientists performed RNA profiling and analysis of samples taken frompancreatic cancer patients. The molecular profiling revealed the same genomicpattern found earlier in mouse models of pancreatic cancer.

Thescientists then devised a novel nanoparticle that selectively delivers geneticmaterial to a tumor and prevents side effects in surrounding healthy tissues.

"Wedesigned a nanocarrier to deliver two passengers: (1) miR-34a, which degradeshundreds of oncogenes; and (2) a PLK1 small interfering RNA (siRNA), thatsilences a single gene," Prof. Satchi-Fainaro says. "These weredelivered directly to the tumor site to change the molecular signature of thecancer cells, rendering the tumor dormant or eradicating it altogether.

"Thenanoparticle is like a taxi carrying two important passengers," Prof.Satchi-Fainaro continues. "Many oncology protocols are cocktails, but thedrugs usually do not reach the tumor at the same time. But our 'taxi' kept the'passengers'—and the rest of the body—safe the whole way, targeting only thetumor tissue. Once it 'parked,' an enzyme present in pancreatic cancer causedthe carrier to biodegrade, allowing the therapeutic cargo to be released at thecorrect address—the tumor cells."

Improvingthe odds

Tovalidate their findings, the scientists injected the novel nanoparticles into pancreatic tumor-bearingmice and observed that by balancing these two targets—bringing them to a normallevel by increasing their expression or blocking the gene responsible for theirexpression—they significantly prolonged the survival of the mice.

"Thistreatment takes into account the entire genomic pattern, and shows thataffecting a single gene is not enough for the treatment of pancreatic cancer orany cancer type in general," according to Prof. Satchi-Fainaro.

Explore further: Newtherapeutic pathway may keep cancer cells turned 'off'

s41467-017-02283-9.pdf