Targeting brain tumor cAMP: the case for sex-specific therapeutics.
Targeting brain tumor cAMP: the case for sex-specific therapeutics.
复制标题
靶向脑肿瘤 cAMP：性别特异性治疗的案例。
DOI：
10.3389/fphar.2015.00153
复制
发表时间：
2015
影响因子：
5.6
通讯作者：
Rubin JB
中科院分区：
文献类型：
--
作者：
Warrington NM;Sun T;Rubin JB
环腺苷酸（cAMP）水平与脑肿瘤生物学之间的关系几乎与cAMP及其合成酶腺苷酸环化酶（ADCY）的已知时间一样长。该途径在脑肿瘤发生中的重要性已在体外和多种动物模型中得到证实。最近，当我们发现ADCY8中的SNP与1型神经纤维瘤病（NF 1）个体中的神经胶质瘤（脑肿瘤）风险相关时，我们为cAMP在脑肿瘤发生中的协同致癌作用提供了人类验证。总之，这些研究为在脑肿瘤治疗中靶向cAMP提供了强有力的理论基础。然而，众所周知，cAMP途径具有性别二态性，ADCY8中的SNP以性别特异性方式影响神经胶质瘤风险，提高女性风险，同时保护男性。cAMP途径在其合成和降解的调节中可以在多个水平上被靶向。对靶向cAMP调节剂的药物反应的性别差异表明，脑肿瘤患者成功靶向cAMP途径可能需要将特定的药物作用机制与患者性别相匹配。
A relationship between cyclic adenosine 3′, 5′-monophosphate (cAMP) levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY) have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor) risk in individuals with Neurofibromatosis type 1 (NF1). Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well-known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex.