Recombinant peptides as biomarkers for tumor response to molecular targeted therapy.
Recombinant peptides as biomarkers for tumor response to molecular targeted therapy.
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DOI：
10.1158/1078-0432.ccr-09-0945
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发表时间：
2009-10-15
期刊：
影响因子：
--
通讯作者：
Diaz R
中科院分区：
文献类型：
--
作者：
Passarella RJ;Zhou L;Phillips JG;Wu H;Hallahan DE;Diaz R
噬菌体展示技术可用于鉴定快速且特异性结合对舒尼替尼治疗有反应的肿瘤的肽序列。这些肽可能有助于解决目前评估肿瘤对治疗反应的方法的问题，这些方法可能很慢并且使用有限。在MDA-MB-231和MCF-7异种移植肿瘤中进行四轮生物淘选后分离感兴趣的肽。用免疫组织化学方法研究肽的结合位置。通过用舒尼替尼处理异种移植有各种肿瘤细胞系的裸鼠，并使用近红外成像来评估与Alexandrin或-750缀合的肽结合肿瘤的能力，来确定其体内结合对治疗有反应的乳腺肿瘤的能力。EGEVGLG是从生物淘选中分离到的优势序列。该肽在对舒尼替尼治疗有反应的两种癌细胞系（MDA-MB-435和MCF-7人乳腺癌）中显示出相对于对照组增加的结合，而当样品与对舒尼替尼治疗无反应的肿瘤细胞（B16黑色素瘤和BxPC 3胰腺癌）一起孵育时，在体外没有发生升高的结合。与未治疗的对照相比，对舒尼替尼治疗有反应的异种移植肿瘤的小鼠显示出增加的肽结合。对舒尼替尼治疗无反应的荷瘤小鼠在治疗组和未治疗组之间未显示肽结合增加。使用重组肽评估癌症的药效学反应有望最大限度地减少患者无效治疗方案的持续时间，可能提供对全身治疗的癌症反应的更快速和侵入性更小的评估。
Phage display technology can be used to identify peptide sequences which bind rapidly and specifically to tumors responding to sunitinib therapy. These peptides may help to address problems with current methods of assessing tumor response to therapy which can be slow and have limited usage. The peptide of interest was isolated after four rounds of biopanning in MDA-MB-231 and MCF-7 xenografted tumors. The peptide’s binding location was investigated with immunohistochemistry. Its in vivo ability to bind to breast tumors responding to therapy was determined by treating nude mice, xenografted with various tumor cell lines, with sunitinib and using near infrared imaging to assess the ability of the peptide conjugated to Alexafluor-750 to bind tumors. EGEVGLG was the dominant sequence isolated from biopanning. This peptide showed increased binding relative to control groups in two cancer cell lines (MDA-MB-435 and MCF-7 human breast) responding to sunitinib treatment while no elevated binding occurred in vitro when samples were incubated with tumor cells that are unresponsive to sunitinib treatment (B16 melanoma and BxPC3 pancreatic). Mice xenografted with tumors that are responsive to sunitinib therapy showed increased peptide binding when compared to untreated control. Mice bearing tumors unresponsive to sunitinib therapy showed no increased peptide binding between treated and untreated groups. The use of recombinant peptides to assess the pharmacodynamic response of cancer holds promise in minimizing the duration of ineffective treatment regimens in patients, potentially providing a more rapid and less invasive assessment of cancer response to systemic therapy.