Paper Details

  1. Home
  2. Paper Details

Quantitative systems pharmacology model-based investigation of adverse gastrointestinal events associated with prolonged treatment with PI3-kinase inhibitors.

Author: DickmannLeslie, FriedrichChristina, GadkarKapil, HurezVincent, JinJin, Kumar JollyMohit, RamanujanSaroja, RuizMaria-Luisa, SchuttLeah, WareJoseph A

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Overview

This study develops a quantitative systems pharmacology model to investigate the development of colitis caused by PI3K inhibitors, which are used to treat various cancers. The model incorporates the effects of different PI3K isoforms on cellular pathways involved in mucosal inflammation and simulates clinical variability in colitis onset and severity. The study suggests that inhibition of both PI3Kδ and PI3Kα contributes to colitis development, highlighting the importance of understanding isoform-specific effects and their interplay in drug-induced adverse events.
Paper Details　
Original Abstract of the Article :
Several PI3K inhibitors are in clinical development for the treatment of various forms of cancers, including pan-PI3K inhibitors targeting all four PI3K isoforms (α, β, γ, and δ), and isoform-selective inhibitors. Diarrhea and immune-mediated colitis are among the adverse events observed with PI3K i...See full text at original site
Dr.Camel IconDr.Camel's Paper Summary Blogラクダ博士について

ラクダ博士は、Health Journal が論文の内容を分かりやすく解説するために作成した架空のキャラクターです。
難解な医学論文を、専門知識のない方にも理解しやすいように、噛み砕いて説明することを目指しています。

* ラクダ博士による解説は、あくまで論文の要点をまとめたものであり、原論文の完全な代替となるものではありません。詳細な内容については、必ず原論文をご参照ください。
* ラクダ博士は架空のキャラクターであり、実際の医学研究者や医療従事者とは一切関係がありません。
* 解説の内容は Health Journal が独自に解釈・作成したものであり、原論文の著者または出版社の見解を反映するものではありません。


引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124351/

データ提供：米国国立医学図書館（NLM）

Decoding the Mystery of PI3K Inhibitor-Induced Colitis

The fight against cancer is a relentless quest, and PI3K inhibitors are potent weapons in this battle. However, like a double-edged sword, these inhibitors can also cause adverse effects, such as diarrhea and colitis. This research delves into the intricate mechanisms behind these gastrointestinal complications, utilizing a quantitative systems pharmacology model to unravel the interplay of different PI3K isoforms and their impact on mucosal inflammation. The study reveals a complex interplay between PI3Kδ, responsible for T cell differentiation and proliferation, and PI3Kα, which regulates epithelial barrier integrity.

The Subtle Dance of PI3K Isoforms: A Tale of Synergy

The study demonstrates that inhibition of PI3Kα below a certain threshold can lead to epithelial barrier dysfunction, exacerbating the T effector response driven by PI3Kδ inhibition. This synergistic effect explains the varying rates of diarrhea and colitis observed with different PI3K inhibitors. The researchers highlight that the specific balance of PI3Kα and PI3Kδ inhibition determines the risk of colitis development, offering valuable insights for optimizing treatment strategies.

A Balancing Act: Navigating the Risks and Benefits

The desert of cancer treatment is fraught with complexities, and finding the right balance is crucial. This research underscores the importance of understanding the intricate interplay of different pathways involved in PI3K inhibitor-induced colitis. By considering the specific roles of PI3Kα and PI3Kδ, clinicians can potentially optimize treatment strategies, minimizing adverse effects while maximizing therapeutic benefits.

Dr.Camel's Conclusion

This research is like a compass guiding us through the complex terrain of cancer treatment. By understanding the intricate dance of PI3K isoforms, we can better navigate the risks and benefits of these powerful drugs, ultimately ensuring a more effective and safer journey for patients.

Date :
  1. Date Completed 2022-05-24
  2. Date Revised 2023-09-16
Further Info :

Pubmed ID

34850607

DOI: Digital Object Identifier

PMC9124351

Related Literature

Article Analysis
・Effects of umbralisib
SNS
PICO Info
in preparation
Languages

English

Positive IndicatorAn AI analysis index that serves as a benchmark for how positive the results of the study are. Note that it is a benchmark and requires careful interpretation and consideration of different perspectives.

This site uses cookies. Visit our privacy policy page or click the link in any footer for more information and to change your preferences.