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Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats

Bianca Facchim Gonçalves1, Silvana Gisele Pegorin de Campos2, Wagner José Fávaro3

  • 1Department of Morphology, Institute of Biosciences, Sao Paulo State University (UNESP), Rua Professor Doutor Antonio Celso Wagner Zanin, 250, Botucatu, SP, 18618-689, Brazil. bianca.fgoncalves@gmail.com.

Hormones & Cancer
|January 25, 2018
PubMed

Insights

Combining abiraterone acetate and NVP-BEZ235 (BEZ235) effectively halts prostate cancer progression. This combination therapy prevents resistance and treats early-stage prostate cancer better than single drugs.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Prostate cancer (PCa) drug resistance necessitates novel therapeutic strategies.
  • Targeting multiple pathways involved in PCa progression is a promising approach.
  • Abiraterone acetate (antiandrogen) and NVP-BEZ235 (PI3K/Akt inhibitor) are potential candidates for combination therapy.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of combining abiraterone acetate and NVP-BEZ235 (BEZ235) in early-stage, androgen-dependent prostate cancer.
  • To compare the combination therapy against monotherapy with either drug.
  • To assess the impact on tumor growth, proliferation, cell death, and inflammatory responses.

Main Methods:

  • Utilized an androgen-dependent prostate cancer model.
  • Administered abiraterone acetate and BEZ235 as monotherapy and in combination.
  • Monitored tumor growth, proliferation, and cell death.
  • Assessed inflammatory responses and lesion progression.

Main Results:

  • Monotherapy with either drug showed limited efficacy, with continued tumor progression and side effects (BEZ235).
  • Combination therapy significantly impaired inflammatory responses and reduced hyperplastic lesions.
  • The combination strategy effectively blocked prostate cancer progression from premalignant to malignant stages.

Conclusions:

  • Blocking both the androgenic and PI3K/AKT/mTOR pathways is an effective therapeutic strategy for prostate cancer.
  • Combination therapy with abiraterone acetate and BEZ235 demonstrates superior outcomes compared to monotherapy.
  • Further investigation of distinct PI3K pathway inhibitors in combination therapies is warranted.

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