The bromodomain and extra-terminal domain inhibitor JQ1 synergistically sensitizes human colorectal cancer cells to topoisomerase I inhibitors through repression of Mre11-mediated DNA repair pathway.

Author: ChenKeling, HeLong, HuWenjun, LeiLinping, LiYuan, LvZhaoying, XieXuqin, ZhouBin, ZhouZongguang

Paper Details 
Original Abstract of the Article :
Camptothecin (CPT) and its derivatives, irinotecan and topotecan are specific topoisomerase I (Top1) inhibitors and potent anticancer drugs. Mechanistically, they induce DNA double-strand breaks (DSBs). Although CPT is an effective chemotherapeutic agent used in the management of advanced colorectal...See full text at original site
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引用元:
https://doi.org/10.1007/s10637-020-01014-0

データ提供:米国国立医学図書館(NLM)

JQ1: A New Ally in the Fight Against Colorectal Cancer

Colorectal cancer, a formidable foe, demands innovative therapeutic strategies. Camptothecin (CPT) and its derivatives, such as irinotecan and topotecan, have emerged as potent topoisomerase I (Top1) inhibitors, effectively inducing DNA double-strand breaks (DSBs). However, these agents can also lead to adverse side effects, necessitating a search for synergistic combinations that enhance efficacy while minimizing toxicity.

This study investigated the potential of JQ1, a bromodomain and extra-terminal domain (BET) inhibitor, as a potential partner in CPT-based chemotherapy for colorectal cancer. Researchers explored the synergistic effects of JQ1 and CPT, examining their impact on cell cycle progression, apoptosis, and DNA repair mechanisms.

Synergy in the Desert: JQ1 and CPT Join Forces

The findings revealed a compelling synergistic effect between JQ1 and CPT, leading to increased cell death, cell cycle arrest, and enhanced sensitivity to CPT in colorectal cancer cells. The authors propose that JQ1's ability to repress the Mre11-mediated DNA repair pathway, a crucial defense mechanism for cancer cells, contributes to this synergistic interaction.

A Promising Future: Exploring New Frontiers in Colorectal Cancer Treatment

This research suggests that the combination of JQ1 and CPT holds promise as a novel therapeutic approach for colorectal cancer. The authors emphasize the need for further investigation to optimize this synergistic combination and translate its potential into clinical benefit. Much like a camel caravan traversing a vast desert, a multidisciplinary approach involving researchers, clinicians, and pharmaceutical companies is essential to realizing the full potential of this promising combination.

Dr. Camel's Conclusion

The fight against colorectal cancer is a challenging journey across a vast desert of uncertainties. This study provides a glimmer of hope, suggesting that JQ1, a new weapon in our arsenal, can work synergistically with CPT to effectively target this formidable foe. By joining forces, we can navigate the terrain of colorectal cancer treatment with renewed optimism and a commitment to improving patient outcomes.

Date :
  1. Date Completed 2022-02-02
  2. Date Revised 2022-02-02
Further Info :

Pubmed ID

32981006

DOI: Digital Object Identifier

10.1007/s10637-020-01014-0

Related Literature

SNS
PICO Info
in preparation
Languages

English

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