Registered report: androgen receptor splice variants determine taxane sensitivity in prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Reproducibility is crucial in scientific research, particularly in prostate cancer.
• The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative aims to address these concerns.
• This report details a replication plan for a key experiment from Thadani-Mulero et al. (2014).

Purpose of the Study:

• To replicate experiments investigating the role of androgen receptor (AR) splice variants in taxane sensitivity.
• To validate findings on how specific AR variants influence response to docetaxel treatment in prostate cancer models.

Main Methods:

• Replication of experiments from Fig. 6A of Thadani-Mulero et al. (2014).
• Generation of xenografts from two prostate cancer cell lines: LuCaP 86.2 (predominantly ARv567) and LuCaP 23.1 (full-length AR and ARv7).
• Treatment of xenografts with the taxane docetaxel to assess tumor growth inhibition.

Main Results:

• Docetaxel inhibited tumor growth in LuCaP 86.2 xenografts, which express the ARv567 splice variant.
• Docetaxel did not significantly inhibit tumor growth in LuCaP 23.1 xenografts, which express full-length AR and ARv7.
• These results suggest a differential sensitivity to taxanes based on AR splice variant expression.

Conclusions:

• The expression of androgen receptor splice variants significantly influences sensitivity to taxane-based chemotherapy in prostate cancer.
• ARv567 may confer sensitivity to docetaxel, while full-length AR and ARv7 may not.
• Replication efforts are vital for confirming findings in prostate cancer research.