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神經素-2（NRP-2），一種與血管內皮細胞生長因子（VEGF）有交互作用的非訊息傳遞穿越細胞膜受體，可能提供了大腸直腸癌治療的新標的；研究者在1月8日國家癌症機構期刊上發表細胞株與動物研究結果，在一篇隨後的主編評論中，這項研究被稱為"破冰研究"。
主編評論是由馬里蘭班塞斯達國家癌症機構Giovanna Tosato醫師與其同事解釋，市場上已經有好幾種抗癌藥物直接針對VEGF，包括人類化單株抗體bevacizumab（Avastin，Genetech/羅氏藥廠）、合成抑制劑sorafenib（Nexavar，拜耳/Onyx藥廠）與sunitinib（Sutent，輝瑞藥廠）；他們評論，這些針對VEGF的治療已經被證實在某些癌症種類上有好處，但效果一般而言是輕微的、延長數個月的癌症存活時間，他們表示，這些經驗引起了許多有關於目前血管新生抑制治療於癌症治療上適當角色的許多問題。
由休士頓德州大學安德森癌症中心的Michael Gray醫師領導的研究者們表示，使用抗神經素-2治療針對與抗VEGF療法可能改善現存抗血管新生治療且可能提供戰勝NRP-2表現腫瘤，例如大腸直腸癌，生長與轉移的獨特機會。
在他們的研究中，Gray與同事們表示，NRP-2在他們所測試大多數人類原發性與轉移性大腸癌樣本中是升高的，但是在人類正常大腸黏膜中卻是正常的；透過動物模式，他們顯示自人類大腸直腸癌細胞分離出來的腫瘤並未表現NRP-2，且較於自表現該受體腫瘤分離出來的腫瘤細胞不容易造成肝臟轉移；除此之外，表現NRP-2的腫瘤會在肝臟與皮下生長，但大小比不表現NRP-2的腫瘤小。
Gray醫師與其同事表示，總而言之，我們已經證實NRP-2表現會延長細胞存活時間、移動、侵入以及活體腫瘤生長，這代表大腸直腸腫瘤細胞生長與蔓延的所有重要部分，且我們的發現顯示，NRP-2可能是大腸直腸癌一項有潛力的治療標的。
主編們表示，這項研究提供了有關於NRP-2扮演角色的"歡迎新訊息"，他們的評論是，讓我們祈禱針對NRP-2的治療方式對於對抗癌症微型生態與癌症本身有加乘的作用。
這項研究由國家衛生研究院與許多獨立癌症研究經費贊助。
Neuropilin-2 May Offer New Therapeutic Target in Colon Cancer
By Zosia Chustecka
Medscape Medical News
Neurolipin-2 (NRP-2), a nonsignaling transmembrane receptor that interacts with vascular endothelial growth factor (VEGF), may offer a promising new therapeutic target in colorectal cancer. So conclude researchers reporting data from cell-line and animal studies published online January 8 in the Journal of the National Cancer Institute. In an accompanying editorial, the research is described as "ground-breaking work."
The editorial, authored by Giovanna Tosato, MD, from the National Cancer Institute, in Bethesda, Maryland, and colleagues, explains that there are already several anticancer drugs on the market that directly target VEGF, including the humanized monoclonal antibody bevacizumab (Avastin, Genentech/Roche) and the synthetic inhibitors sorafenib (Nexavar, Bayer/Onyx) and sunitinib (Sutent, Pfizer). "These VEGF-targeted therapies have shown benefit in certain cancer types, but the responses have generally been modest and measured in months of extended cancer survival," they comment. "This experience raises many questions regarding the appropriate role of current antiangiogenic therapies in cancer treatment," they add.
The researchers, led by Michael Gray, MD, from the University of Texas M.D. Anderson Cancer Centre, in Houston, suggest that "the use of anti–neuropilin-2 therapeutic targeting in conjunction with anti-VEGF therapy may improve on existing angiogenesis treatments and may provide a unique opportunity to circumvent the ability of NRP-2-expressing tumors, such as colorectal cancers, to grow and metastasize."
In their studies, Dr. Gray and colleagues showed that NRP-2 was elevated in most of the human primary and metastatic colon cancer specimens they tested but was not elevated in normal human colonic mucosa. The receptor was also expressed in most of the human colorectal cancer cell lines tested. Using mice, they showed that tumors derived from human colorectal cancer cells that did not express NRP-2 were less capable of establishing liver metastases than tumors derived from cells lines that did express the receptor. Also, the tumors expressing NRP-2 that did grow, both in the liver and subcutaneously, were smaller than the tumors that did not express NRP-2.
"In summary, we have shown that NRP-2 expression enhances cell survival, migration, invasion, and in vivo tumor growth — all critical aspects of colorectal cancer growth and progression — and our findings suggest that NRP-2 may be a promising therapeutic target for colorectal cancer," Dr. Gray and colleagues conclude.
The editorialists add that the study provides "welcome new information" about the role played by NRP-2. "Let us hope that targeting neuropilin-2 can hit double punches against the cancer microenvironment and the cancer itself," they comment.
The study was funded by grants from the National Institutes of Health and several independent cancer research funds.
J Natl Cancer Inst. 2008;100:109-120 Abstract, 81-83. Abstract