scholarly journals Identification of potent SENP1 inhibitors that inactivate SENP1/JAK2/STAT signaling pathway and overcome platinum drug resistance in ovarian cancer

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Yi Zhang ◽  
Huiqiang Wei ◽  
Yuan Zhou ◽  
Zhuqing Li ◽  
Wenfeng Gou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
Platinum Drug ◽  
Stat Signaling ◽  
Platinum Drug Resistance

Nanoparticle-based drug delivery systems with platinum drugs for overcoming cancer drug resistance

2021 ◽  
Author(s):  
Peng Xie ◽  
Yushu Wang ◽  
Dengshuai Wei ◽  
Lingpu Zhang ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Cancer Drug ◽  
Platinum Drugs ◽  
Effective Strategy ◽  
Platinum Drug ◽  
Cancer Drug Resistance ◽  
Platinum Drug Resistance

The mechanisms of chemoresistance and nanoparticle-based drug delivery systems for platinum drugs were detailed summarized in this review. The current combination therapy provided an effective strategy to overcome the platinum drug resistance.

scholarly journals SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jing Li ◽  
Ruiqin Wu ◽  
Mingo M. H. Yung ◽  
Jing Sun ◽  
Zhuqing Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Kinase Activity ◽  
Regulatory Mechanism ◽  
Platinum Resistance ◽  
Platinum Drug ◽  
Clinical Prognosis ◽  
Platinum Resistant ◽  
Poor Clinical Prognosis ◽  
Stat Pathway

AbstractThe JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.

scholarly journals Somatic Mutation Profiling of Intrahepatic Cholangiocarcinoma: Comparison between Primary and Metastasis Tumor Tissues

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Shi-Feng Xu ◽  
Yuan Guo ◽  
Xin Zhang ◽  
Xiao-Dan Zhu ◽  
Ning Fan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Intrahepatic Cholangiocarcinoma ◽  
Notch Pathway ◽  
Treatment Strategies ◽  
Immune Gene ◽  
Platinum Drug ◽  
Clinical Prognosis ◽  
Resistance Pathway ◽  
Incidence And Mortality ◽  
Platinum Drug Resistance

Introduction. Intrahepatic cholangiocarcinoma (ICC) exhibited increasing incidence and mortality around the world, with a 35% five-year survival rate. In this study, the genetic alteration of primary ICC and metastasis ICC was exhibited to discover novel personalized treatment strategies to improve the clinical prognosis. Methods. Based on 153 primary and 49 metastasis formalin-fixed paraffin-embedded ICC samples, comprehensive genomic profiling was carried out. Results. In primary tumor samples (PSs) and metastasis tumor samples (MSs), the top alteration genes were TP53 (41.8% vs 36.7%), KRAS (30.7% vs 36.7%), and ARID1A (22.2% vs 14.2%). In the top 20 most frequent alteration genes, BRAF showed lower mutation frequency in MSs as compared to PSs (0 vs 11.1%, P=0.015), while LRP1B exhibited opposed trend (22.4% vs 10.4%, P=0.032). In PSs, patients with MSI-H showed all PDL1 negative, and patients with PDL1 positive exhibited MSS both in PSs and MSs. It was found that the Notch pathway had more alteration genes in MSI-H patients (P=0.027). Furthermore, the patients with mutated immune genes in PSs were more than that in MSs (28.8% vs 8.2%, P=0.003, odd ratio = 0.2). Interestingly, the platinum drug resistance pathway was only enriched by mutated genes of MSs. Conclusions. In this study, the identification of two meaningful mutated genes, BRAF and LRP1B, highly mutated immune gene harbored by primary ICC patients. Both in PSs and MSs, no patients with MSI-H showed PDL1 positive. The Notch pathway had more alteration genes in patients with MSI-H. And the enrichment of the platinum drug resistance pathway in MSs might offer reference for the novel therapeutic strategy of ICC.

Biodegradable polymer–platinum drug conjugates to overcome platinum drug resistance

RSC Advances ◽  
2015 ◽  
Vol 5 (101) ◽  
pp. 83343-83349 ◽  
Author(s):  
Qiang Yang ◽  
Ruogu Qi ◽  
Jing Cai ◽  
Xiang Kang ◽  
Si Sun ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Carboxylic Acids ◽  
Biodegradable Polymers ◽  
Biodegradable Polymer ◽  
Platinum Drug ◽  
Drug Conjugates ◽  
Self Assembled ◽  
Platinum Drug Resistance

Biodegradable polymers with pendent pair-wised carboxylic acids but lacking sulfur were used to chelate oxaliplatin prodrug which self-assembled into micelles in water for drug delivery.

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