Prostate-specific antigen dynamics predict individual responses to intermittent androgen deprivation

Brady‐Nicholls, Renee; Nagy, John D.; Gerke, Travis; Zhang, Tian; Wang, Andrew Z.; Zhang, Jingsong; Gatenby, Robert A.; Enderling, Heiko

doi:10.1038/s41467-020-15424-4

Cited by 81 publications

(77 citation statements)

References 45 publications

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“…Pgp allocrites are amphiphilic and either electrically neutral or cationic. phenotypes are able to proliferate extensively, a process governed by eco-evolutionary dynamics (1,88).…”

Section: Pgp In Immunosurveillancementioning

confidence: 99%

P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers

Seelig

2020

Front. Oncol.

129

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P-glycoprotein or multidrug resistance protein (MDR1) is an adenosine triphosphate (ATP) binding cassette transporter (ABCB1) intensely investigated because it is an obstacle to successful pharmacotherapy of cancers. P-glycoprotein prevents cellular uptake of a large number of structurally and functionally diverse compounds, including most cancer therapeutics and in this way causes multidrug resistance (MDR). To overcome MDR, and thus improve cancer treatment, an understanding of P-glycoprotein inhibition at the molecular level is required. With this goal in mind, we propose rules that predict whether a compound is a modulator, substrate, inhibitor, or inducer of P-glycoprotein. This new set of rules is derived from a quantitative analysis of the drug binding and transport properties of P-glycoprotein. We further discuss the role of P-glycoprotein in immune surveillance and cell metabolism. Finally, the predictive power of the proposed rules is demonstrated with a set of FDA approved drugs which have been repurposed for cancer therapy.

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“…Pgp allocrites are amphiphilic and either electrically neutral or cationic. phenotypes are able to proliferate extensively, a process governed by eco-evolutionary dynamics (1,88).…”

Section: Pgp In Immunosurveillancementioning

confidence: 99%

P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers

Seelig

2020

Front. Oncol.

129

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“…In a retrospective study, Buttigliero et al[ 75 ] showed that early PSA drop was related to a better overall survival and progression-free survival in mCRPC patients treated with abiraterone or enzalutamide (docetaxel-naïve or post-docetaxel setting). Finally, a mathematical model of PSA dynamics has been proposed to predict individual response to intermittent androgen deprivation therapy[ 76 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Circulating cell-free nucleic acids as prognostic and therapy predictive tools for metastatic castrate-resistant prostate cancer

Sobhani¹,

Sirico²,

Generali³

et al. 2020

WJCO

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Metastatic castrate-resistant prostate cancer remains a disease hard to cure, and for this reason predictive tools to monitor disease progression and therapy response are an urgent need. In this respect, liquid biopsy on circulating cell-free nucleic acids represents an interesting strategy based on robust data. The low invasiveness and the possibility to target circulating cell-free tumor deoxyribonucleic acid underline the high specificity, sensitivity and clinical usability of the technique. Moreover, it has been observed that the cell-free tumor deoxyribonucleic acid of metastatic castrate-resistant prostate cancer patients can be representative of the tumor heterogeneity. Cell-free tumor deoxyribonucleic acids express the same behaviors as mutations: Variation in gene copy number or the methylation rate of the tumor tissue. Recently, circulating cell-free ribonucleic acid molecules have emerged as interesting markers to stratify the disease. Due to high-throughput technologies, liquid biopsy on circulating cell-free nucleic acids will soon be utilized in the clinical management of metastatic castrate-resistant prostate cancer patients.

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“…West et al developed an evolutionary game theory model to determine the optimal timing of multi-drug adaptive therapies [ 23 ]. Brady-Nicholls et al developed patient-specific mathematical models that explain prostate cancer inter-tumor dynamics that can guide intermittent androgen deprivation therapy [ 24 ]. Mathematical modeling has shown the consequences of having spontaneous versus induced resistance responses to therapy [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Adaptive Therapy for Metastatic Melanoma: Predictions from Patient Calibrated Mathematical Models

Kim

Brown

Eroglu

et al. 2021

Cancers

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Adaptive therapy is an evolution-based treatment approach that aims to maintain tumor volume by employing minimum effective drug doses or timed drug holidays. For successful adaptive therapy outcomes, it is critical to find the optimal timing of treatment switch points in a patient-specific manner. Here we develop a combination of mathematical models that examine interactions between drug-sensitive and resistant cells to facilitate melanoma adaptive therapy dosing and switch time points. The first model assumes genetically fixed drug-sensitive and -resistant popul tions that compete for limited resources. The second model considers phenotypic switching between drug-sensitive and -resistant cells. We calibrated each model to fit melanoma patient biomarker changes over time and predicted patient-specific adaptive therapy schedules. Overall, the models predict that adaptive therapy would have delayed time to progression by 6−25 months compared to continuous therapy with dose rates of 6−74% relative to continuous therapy. We identified predictive factors driving the clinical time gained by adaptive therapy, such as the number of initial sensitive cells, competitive effect, switching rate from resistant to sensitive cells, and sensitive cell growth rate. This study highlights that there is a range of potential patient-specific benefits of adaptive therapy and identifies parameters that modulate this benefit.

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Prostate-specific antigen dynamics predict individual responses to intermittent androgen deprivation

Cited by 81 publications

References 45 publications

P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers

P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers

Circulating cell-free nucleic acids as prognostic and therapy predictive tools for metastatic castrate-resistant prostate cancer

Adaptive Therapy for Metastatic Melanoma: Predictions from Patient Calibrated Mathematical Models

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