A two-drug combination simulation study for metastatic castrate resistant prostate cancer

The Prostate
Alex Root, H Alexander Ebhardt

Abstract

Prostate cancer often evolves resistance to androgen deprivation therapy leading to a lethal metastatic castrate-resistant form. Besides androgen independence, subpopulations of the tumor are genetically heterogeneous. With the advent of tumor genome sequencing we asked which has the greater influence on reducing tumor size: genetic background, heterogeneity, or drug potency? A previously developed theoretical evolutionary dynamics model of stochastic branching processes is applied to compute the probability of tumor eradication with two targeted drugs. Publicly available data sets were surveyed to parameterize the model. Our calculations reveal that the greatest influence on successful treatment is the genetic background including the number of mutations overcoming resistance. Another important criteria is the tumor size at which it is still possible to achieve tumor eradication, for example, 2-4 cm large tumors have at best a 10% probability to be eradicated when 50 mutations can confer resistance to each drug. Overall, this study finds that genetic background and tumor heterogeneity are more important than drug potency in treating mCRPC. It also points toward identifying metastatic sites early using biochemical assays and/or...Continue Reading

References

Jun 25, 2009·Cancer Research·Mark M PomerantzMatthew L Freedman
Jun 15, 2012·Nature Reviews. Cancer·Robert J GilliesRobert A Gatenby
Jul 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Haley HieronymusCharles L Sawyers
Apr 16, 2016·Asian Journal of Andrology·Jonathan Shoag, Christopher E Barbieri
Jun 2, 2016·Nature Reviews. Clinical Oncology·Daniel E SprattScott A Tomlins
Aug 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Anat ZimmerUri Alon
May 28, 2017·Journal of Vascular and Interventional Radiology : JVIR·Michael G HolmesThomas M Link
Nov 29, 2017·Nature Communications·Jingsong ZhangRobert A Gatenby
Jul 7, 2018·NPJ Systems Biology and Applications·H Alexander EbhardtRuedi Aebersold

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Urology
Christopher J Logothetis
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Jeffrey B WestRobert A Gatenby
Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Z J Khamis, T Merali
© 2022 Meta ULC. All rights reserved