What question did this study set out to answer?

To identify molecular alterations in prostate carcinomas exposed to neoadjuvant chemotherapy in vivo and evaluate their functional role in mediating drug resistance.

October 1, 2007Clinical Cancer Research

Molecular Alterations in Prostate Carcinomas that Associate with In vivo Exposure to Chemotherapy: Identification of a Cytoprotective Mechanism Involving Growth Differentiation Factor 15

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Authors

CHChung-Ying HuangChang Gung University TBTomasz M. BeerOregon Health & Science University CHCelestia S. HiganoUniversité Paris-Sud

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Implication

Phase II trial reveals chemotherapy-induced GDF15 expression conferring drug resistance in prostate cancer, highlighting a potential target for sensitizing tumors.

Key Points

To identify molecular alterations in prostate carcinomas exposed to neoadjuvant chemotherapy in vivo and evaluate their functional role in mediating drug resistance.
Enrolled patients with high-risk localized prostate cancer (TNM ≥ T2b, PSA ≥ 15 ng/mL, or Gleason grade ≥ 4+3) into a phase II trial of neoadjuvant docetaxel and mitoxantrone followed by prostatectomy.
Collected pre-treatment needle biopsies and post-treatment prostatectomy tissues from 31 patients completing four chemotherapy cycles, isolating prostate epithelium via microdissection for cDNA microarray profiling and RT-qPCR validation.
Conducted in vitro assays by overexpressing GDF15 or exposing prostate cancer cell lines to exogenous recombinant GDF15 during docetaxel and mitoxantrone treatment.
Identified 51 genes with significant transcript level alterations following chemotherapy after adjusting for prostatectomy-induced artifacts, including cytokines GDF15, CXCL10, and IL1R1.
Demonstrated that both ectopic overexpression of GDF15 and direct exposure to recombinant GDF15 conferred cellular resistance to docetaxel and mitoxantrone in prostate cancer cell lines.

Cite This Study

Huang et al. (2007) studied this question.

synapsesocial.com/papers/6a6fa648af0c21e93927aaa8 https://doi.org/10.1158/1078-0432.ccr-07-1037

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Implication

Phase II trial reveals chemotherapy-induced GDF15 expression conferring drug resistance in prostate cancer, highlighting a potential target for sensitizing tumors.

Molecular Alterations in Prostate Carcinomas that Associate with In vivo Exposure to Chemotherapy: Identification of a Cytoprotective Mechanism Involving Growth Differentiation Factor 15

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Cite This Study

Molecular Alterations in Prostate Carcinomas that Associate with In vivo Exposure to Chemotherapy: Identification of a Cytoprotective Mechanism Involving Growth Differentiation Factor 15

Discussion

Member takes

Implication

Key Points

Cite This Study

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