Insulin-like growth factor pathway: A link between androgen deprivation therapy (ADT), insulin resistance, and disease progression in patients with prostate cancer?

2013 ◽  
Vol 31 (5) ◽  
pp. 522-530 ◽  
Author(s):  
Rahul R. Aggarwal ◽  
Charles J. Ryan ◽  
June M. Chan
Author(s):  
George Yu ◽  
Abdulmaged M. Traish

AbstractOver the past 60 years, androgen deprivation therapy has been the mainstay of treatment of metastatic prostate cancer. However, research findings suggest that androgen deprivation therapy inflicts serious adverse effects on overall health and reduces the quality of life. Among the adverse effects known to date are insulin resistance, diabetes, metabolic syndrome fatigue, erectile dysfunction, and cardiovascular disease. In this clinical perspective, we discuss the relationship between induced androgen deficiency and a host of pathologies in the course of treatment with androgen deprivation therapy for prostate cancer patients.


2020 ◽  
pp. 100-108
Author(s):  
I. G. Rusakov ◽  
A. A. Gritskevich ◽  
T. P. Baitman ◽  
S. V. Mishugin

This review is dedicated to the impact of modern achievements on the definition and diagnostics of castration-resistant prostate cancer (PCa) (CRPC), prognostic factors for its progression, and treatment strategies.It was proven with new sensitive methods of diagnostics that surgical castration (CS) decreases serum testosterone (T) levels to < 20 ng/dL, while achieving T < 20 ng/dL improves outcomes and delays the development of CRPC. Regular assessment of the T level makes it possible to understand whether this androgen is adequately suppressed in the setting of potential progression of CRPC, given that late dosing may lead to an increase in T level. Improved imaging techniques and biomarker analysis enable early detection of disease progression. Prognostically significant risk factors for CRPC progression include Gleason score, the extent of metastatic spread, hereditary characteristics such as gene mutations affecting androgen receptor (AR) amplification or DNA repair deficiency mutations, prostate-specific antigen (PSA) kinetics, and biomarker levels. Today, treatment options for CRPC have gone beyond androgen deprivation therapy (ADT) to include therapy that blocks T-synthesis and/or suppresses its activity through various mechanisms. Future directions include therapies using new biological targets, drug combinations and personalized therapies. It is necessary to assess the possible reasons for the difference in the pharmacodynamics and pharmacokinetics of androgendeprivation drugs, to study the features of the processes of destruction of drugs under the action of endogenous enzymes and resorption in the subcutaneous or muscle depot, which may cause the resistance to therapy.The aim of improved treatment and diagnostic options for PCa is to delay its progression to CRPC and to prolong patient survival. Rethinking of the castration concept and advances in understanding the biology of disease progression make it necessary to revise diagnostic and treatment strategies. ADT is a fundamental vector of treatment, and it should be continued even if some new ways of treatment for CRPC are introduced.


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