Body composition as a determinant of the therapeutic index with androgen signaling inhibition.

Autor: Hahn AW; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ahahn@mdanderson.org., Tidwell RS; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pilie PG; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Yu Y; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Liu J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Surasi DS; Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Titus M; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Venkatesh N; Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA., Panaretakis T; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gregg JR; Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zurita AJ; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Siddiqui BA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Corn PG; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Subudhi SK; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Msaouel P; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, USA., Koutroumpakis E; Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Huff CD; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Aparicio A; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., McQuade JL; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Frigo DE; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Logothetis CJ; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, USA.
Jazyk: angličtina
Zdroj: Prostate cancer and prostatic diseases [Prostate Cancer Prostatic Dis] 2024 Jul 17. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1038/s41391-024-00870-8
Abstrakt: Background: Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI. We hypothesized that host adiposity and androgen synthesis are linked to the efficacy and toxicity of ASI for men with metastatic castration-resistant prostate cancer (mCRPC).
Methods: A post-hoc analysis was done of NCT02703623 where men with mCRPC (n = 186) were treated for 8 weeks with abiraterone acetate, prednisone, and apalutamide (AAPA), and a satisfactory response was defined as a PSA decline >50%. Body composition was measured on baseline CT scans. Germline DNA WES was performed with a focus on variants in steroidogenic genes. Adipokine levels were measured in pre-treatment plasma.
Results: Germline polymorphisms in 3 genes involved in androgen synthesis (AKR1C3 rs12529, CYP17A1 rs6162, SRD5A2 rs523349) were associated with differences in body composition at baseline on ADT alone (prior to receipt of AAPA). Elevated subcutaneous adipose tissue index (SATi, p = 0.02), visceral adipose tissue index (VATi, p = 0.03), and BMI (p = 0.04) were associated with satisfactory response to AAPA. Leptin had positive correlation with VATi (r = 0.47) and SATi (r = 0.48).
Conclusion: Inherited polymorphisms in androgen synthesis correlated with differences in body composition after exposure to ADT and warrant further investigation as candidate markers for body composition toxicity. Elevated subcutaneous and visceral adiposity were associated with improved response to ASI.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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