Clinical & Experimental Metastasis

, Volume 31, Issue 8, pp 991–999 | Cite as

Improving treatment strategies for patients with metastatic castrate resistant prostate cancer through personalized computational modeling

  • Jill Gallaher
  • Leah M. Cook
  • Shilpa Gupta
  • Arturo Araujo
  • Jasreman Dhillon
  • Jong Y. Park
  • Jacob G. Scott
  • Julio Pow-Sang
  • David Basanta
  • Conor C. Lynch
Review

Abstract

Metastatic castrate resistant prostate cancer (mCRPC) is responsible for the majority of prostate cancer deaths with the median survival after diagnosis being 2 years. The metastatic lesions often arise in the skeleton, and current treatment options are primarily palliative. Using guidelines set forth by the National Comprehensive Cancer Network (NCCN), the medical oncologist has a number of choices available to treat the metastases. However, the sequence of those treatments is largely dependent on the patient history, treatment response and preferences. We posit that the utilization of personalized computational models and treatment optimization algorithms based on patient specific parameters could significantly enhance the oncologist’s ability to choose an optimized sequence of available therapies to maximize overall survival. In this perspective, we used an integrated team approach involving clinicians, researchers, and mathematicians, to generate an example of how computational models and genetic algorithms can be utilized to predict the response of heterogeneous mCRPCs in bone to varying sequences of standard and targeted therapies. The refinement and evolution of these powerful models will be critical for extending the overall survival of men diagnosed with mCRPC.

Keywords

Metastatic castrate resistant prostate cancer Bone metastasis Computational biology Genetic algorithms Heterogeneity Therapy sequence optimization Overall survival 

List of abbreviations

ADT

Androgen deprivation therapy

AR

Androgen receptor

GA

Genetic algorithm

JAK/STAT

Janus kinase/Signal transducers and activators of transcription

mCRPC

Metastatic castrate resistant prostate cancer

NCCN

National comprehensive cancer network

ODE

Ordinary differential equation

PSA

Prostate serum antigen

PTEN

Phosphatase and tensin homolog

RANKL

Receptor activator of nuclear kappa B ligand

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Jill Gallaher
    • 1
  • Leah M. Cook
    • 2
  • Shilpa Gupta
    • 3
  • Arturo Araujo
    • 1
  • Jasreman Dhillon
    • 3
  • Jong Y. Park
    • 4
  • Jacob G. Scott
    • 1
    • 5
  • Julio Pow-Sang
    • 3
  • David Basanta
    • 1
  • Conor C. Lynch
    • 2
  1. 1.Department of Integrated Mathematical Oncology, SRBH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Tumor Biology Department, SRBH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  3. 3.Department of Genitourinary OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  4. 4.Department of Cancer EpidemiologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  5. 5.Wolfson Center for Mathematical BiologyMathematical Institute, University of OxfordOxfordUK

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