Cancers, Vol. 13, Pages 3737: Targeting RB1 Loss in Cancers
Cancers, Vol. 13, Pages 3737: Targeting RB1 Loss in Cancers
Cancers doi: 10.3390/cancers13153737
Authors:
Paing Linn
Susumu Kohno
Jindan Sheng
Nilakshi Kulathunga
Hai Yu
Zhiheng Zhang
Dominic Voon
Yoshihiro Watanabe
Chiaki Takahashi
Retinoblastoma protein 1 (RB1) is encoded by a tumor suppressor gene that was discovered more than 30 years ago. Almost all mitogenic signals promote cell cycle progression by braking on the function of RB1 protein through mono- and subsequent hyper-phosphorylation mediated by cyclin-CDK complexes. The loss of RB1 function drives tumorigenesis in limited types of malignancies including retinoblastoma and small cell lung cancer. In a majority of human cancers, RB1 function is suppressed during tumor progression through various mechanisms. The latter gives rise to the acquisition of various phenotypes that confer malignant progression. The RB1-targeted molecules involved in such phenotypic changes are good quarries for cancer therapy. Indeed, a variety of novel therapies have been proposed to target RB1 loss. In particular, the inhibition of a number of mitotic kinases appeared to be synthetic lethal with RB1 deficiency. A recent study focusing on a neighboring gene that is often collaterally deleted together with RB1 revealed a pharmacologically targetable vulnerability in RB1-deficient cancers. Here we summarize current understanding on possible therapeutic approaches targeting functional or genomic aberration of RB1 in can...
Source: Cancers - Category: Cancer & Oncology Authors: Paing Linn Susumu Kohno Jindan Sheng Nilakshi Kulathunga Hai Yu Zhiheng Zhang Dominic Voon Yoshihiro Watanabe Chiaki Takahashi Tags: Review Source Type: research
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