2020
DOI: 10.1016/j.ccell.2019.11.003
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CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer

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Cited by 151 publications
(142 citation statements)
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“…Then, we showed that THZ1 sensitized tumors to antiPD-1 antibodies in vivo by decreasing PD-L1 expression and recruiting infiltrating CD8 + T cells which drive the antitumor immunity response [25]. A recent study showed that CDK7 inhibitor YKL-5-124 causes DNA damage in small cell lung cancer (SCLC) and sensitizes tumors to antiPD-1 therapy by provoking a robust immune surveillance program elicited by T cells [52]. In contrast to THZ1, YKL-5-124 treatment had no effect on CTD phosphorylation of RNA Pol II, indicating that YKL-5-124 does not inhibit global transcription.…”
Section: Discussionmentioning
confidence: 99%
“…Then, we showed that THZ1 sensitized tumors to antiPD-1 antibodies in vivo by decreasing PD-L1 expression and recruiting infiltrating CD8 + T cells which drive the antitumor immunity response [25]. A recent study showed that CDK7 inhibitor YKL-5-124 causes DNA damage in small cell lung cancer (SCLC) and sensitizes tumors to antiPD-1 therapy by provoking a robust immune surveillance program elicited by T cells [52]. In contrast to THZ1, YKL-5-124 treatment had no effect on CTD phosphorylation of RNA Pol II, indicating that YKL-5-124 does not inhibit global transcription.…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, the combination of a CHK1 inhibitor and low dose gemcitabine enhanced the effect of PD-L1 inhibition (45), and concomitant treatment with a DDR inhibitor remarkably potentiated the antitumor effects of PD-L1 inhibition in mouse models of SCLC (46). Treatment with a cyclin-dependent kinase 7 inhibitor, YKL-5-124, was also found to enhance anti-tumor efficacy of a PD-1 inhibitor in SCLC preclinical models (47). Several clinical trials using immune checkpoint inhibitor combinations are ongoing (48).…”
Section: Immunotherapy Regimens and Combinations For Sclcmentioning
confidence: 94%
“…Recent work has highlighted the potential of CDK7 inhibitors to be used in combination with immunotherapies. The CDK7 inhibitor, YKL-5-124, was shown to elicit immune response signalling in small cell lung cancer (SCLC), activating anti-tumourigenic T cells [131]. In immunocompetent mouse models of SCLC, the combination of YKL-5-124 and anti-PD-1 immune checkpoint inhibition increased overall survival in comparison with either treatment alone, and was further enhanced by the addition of chemotherapeutics (cisplatin and etoposide) [131].…”
Section: B E T I N H I B I T O R S C O M P O U N D S T H a T T A Rmentioning
confidence: 99%