The human proton-coupled folate transporter: Biology and therapeutic applications to cancer.
The human proton-coupled folate transporter: Biology and therapeutic applications to cancer.
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DOI：
10.4161/cbt.22020
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发表时间：
2012-12
影响因子：
3.6
通讯作者：
Matherly LH
中科院分区：
文献类型：
--
作者：
Desmoulin SK;Hou Z;Gangjee A;Matherly LH
本文综述了质子偶联叶酸转运蛋白（PCFT）的生物学。PCFT在2006年被确定为膳食叶酸的肠道吸收的主要转运蛋白，因为PCFT的突变是遗传性叶酸吸收不良（HFM）综合征的原因。自2006年以来，在理解PCFT蛋白中的关键氨基酸和/或结构域的机制作用方面取得了重大进展，其中许多在HFM患者中被鉴定为突变的，并且在表征人PCFT基因的转录控制方面取得了重大进展。随着认识到PCFT在人类肿瘤中大量表达并且在表征肿瘤微环境的pH下具有活性，注意力转向利用PCFT递送用于实体瘤的新型细胞毒性抗叶酸剂。培美曲塞是一种极好的PCFT底物，这一发现解释了其对间皮瘤和非小细胞肺癌的临床疗效，并促使开发了更具PCFT选择性的肿瘤靶向6-取代吡咯并[2，3-d]嘧啶抗叶酸剂，这些抗叶酸剂通过靶向从头嘌呤核苷酸生物合成产生细胞毒性作用。
This review summarizes the biology of the proton-coupled folate transporter (PCFT). PCFT was identified in 2006 as the primary transporter for intestinal absorption of dietary folates, as mutations in PCFT are causal in hereditary folate malabsorption (HFM) syndrome. Since 2006, there have been major advances in understanding the mechanistic roles of critical amino acids and/or domains in the PCFT protein, many of which were identified as mutated in HFM patients, and in characterizing transcriptional control of the human PCFT gene. With the recognition that PCFT is abundantly expressed in human tumors and is active at pHs characterizing the tumor microenvironment, attention turned to exploiting PCFT for delivering novel cytotoxic antifolates for solid tumors. The finding that pemetrexed is an excellent PCFT substrate explains its demonstrated clinical efficacy for mesothelioma and non-small cell lung cancer, and prompted development of more PCFT-selective tumor-targeted 6-substituted pyrrolo[2,3-d]pyrimidine antifolates that derive their cytotoxic effects by targeting de novo purine nucleotide biosynthesis.
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DOI：
10.1124/jpet.106.104364
发表时间：
2006-08-01
影响因子：
3.5
作者：
Badagnani, Ilaria;Castro, Richard A.;Giacomini, Kathleen M.
通讯作者：
Giacomini, Kathleen M.
影响因子：
4.8
作者：
Bronder, JL;Moran, RG
通讯作者：
Moran, RG
影响因子：
4.8
作者：
Chancy, CD;Kekuda, R;Smith, SB
通讯作者：
Smith, SB
影响因子：
3.4
作者：
Boritzki, TJ;Barlett, CA;Jackson, RC
通讯作者：
Jackson, RC
影响因子：
3
作者：
Budman, DR;Johnson, R;Walling, J
通讯作者：
Walling, J