We have located links that may give you full text access.
Journal Article
Review
Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study.
Recent clinical successes of immune checkpoint modulators have unleashed a wave of enthusiasm associated with cancer immunotherapy. However, this enthusiasm is dampened by persistent translational hurdles associated with cancer immunotherapy that mirror the broader pharmaceutical industry. Specifically, the challenges associated with drug discovery and development stem from an incomplete understanding of the biological mechanisms in humans that are targeted by a potential drug and the financial implications of clinical failures. Sustaining progress in expanding the clinical benefit provided by cancer immunotherapy requires reliably identifying new mechanisms of action. Along these lines, quantitative and systems pharmacology (QSP) has been proposed as a means to invigorate the drug discovery and development process. In this review, I discuss two central themes of QSP as applied in the context of cancer immunotherapy. The first theme focuses on a network-centric view of biology as a contrast to a "one-gene, one-receptor, one-mechanism" paradigm prevalent in contemporary drug discovery and development. This theme has been enabled by the advances in wet-lab capabilities to assay biological systems at increasing breadth and resolution. The second theme focuses on integrating mechanistic modeling and simulation with quantitative wet-lab studies. Drawing from recent QSP examples, large-scale mechanistic models that integrate phenotypic signaling-, cellular-, and tissue-level behaviors have the potential to lower many of the translational hurdles associated with cancer immunotherapy. These include prioritizing immunotherapies, developing mechanistic biomarkers that stratify patient populations and that reflect the underlying strength and dynamics of a protective host immune response, and facilitate explicit sharing of our understanding of the underlying biology using mechanistic models as vehicles for dialogue. However, creating such models require a modular approach that assumes that the biological networks remain similar in health and disease. As oncogenesis is associated with re-wiring of these biological networks, I also describe an approach that combines mechanistic modeling with quantitative wet-lab experiments to identify ways in which malignant cells alter these networks, using Interleukin-12 as an example. Collectively, QSP represents a new holistic approach that may have profound implications for how translational science is performed.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
Perioperative echocardiographic strain analysis: what anesthesiologists should know.Canadian Journal of Anaesthesia 2024 April 11
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app