Elix Catherine, Pal Sumanta K, Jones Jeremy O
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA91010, USA.
Asian J Androl. 2018 May-Jun;20(3):238-243. doi: 10.4103/aja.aja_15_17.
Despite great progress in the detection and treatment of prostate cancer, this disease remains an incredible health and economic burden. Although androgen receptor (AR) signaling plays a key role in the development and progression of prostate cancer, aberrations in other molecular pathways also contribute to the disease, making it essential to identify and develop drugs against novel targets, both for the prevention and treatment of prostate cancer. One promising target is the peroxisome proliferator-activated receptor gamma (PPARγ) protein. PPARγ was originally thought to act as a tumor suppressor in prostate cells because agonist ligands inhibited the growth of prostate cancer cells; however, additional studies found that PPARγ agonists inhibit cell growth independent of PPARγ. Furthermore, PPARγ expression increases with cancer grade/stage, which would suggest that it is not a tumor suppressor but instead that PPARγ activity may play a role in prostate cancer development and/or progression. Indeed, two new studies, taking vastly different, unbiased approaches, have identified PPARγ as a target in prostate cancer and suggest that PPARγ inhibition might be useful in prostate cancer prevention and treatment. These findings could lead to a new therapeutic weapon in the fight against prostate cancer.
尽管在前列腺癌的检测和治疗方面取得了巨大进展,但这种疾病仍然是一个令人难以置信的健康和经济负担。虽然雄激素受体(AR)信号通路在前列腺癌的发生和发展中起关键作用,但其他分子途径的异常也会导致这种疾病,这使得识别和开发针对新靶点的药物对于前列腺癌的预防和治疗至关重要。一个有前景的靶点是过氧化物酶体增殖物激活受体γ(PPARγ)蛋白。PPARγ最初被认为在前列腺细胞中起肿瘤抑制作用,因为激动剂配体可抑制前列腺癌细胞的生长;然而,更多研究发现PPARγ激动剂独立于PPARγ抑制细胞生长。此外,PPARγ的表达随着癌症分级/分期增加,这表明它不是肿瘤抑制因子,而是PPARγ活性可能在前列腺癌的发生和/或发展中起作用。事实上,两项采用截然不同的无偏倚方法的新研究已将PPARγ确定为前列腺癌的一个靶点,并表明抑制PPARγ可能有助于前列腺癌的预防和治疗。这些发现可能会为抗击前列腺癌带来一种新的治疗武器。