Anti-mitotic agent SB-216 overcomes taxane resistance in castration-resistant prostate cancer and exhibits anti-tumour efficacy in pancreatic cancer

  • Br J Pharmacol. 2025 Dec 17. doi: 10.1111/bph.70294.
Rui Wang  1  2 ,  Chun Cai  3  4 ,  Shanshan Deng  2 ,  Yang Xie  1 ,  Satyanarayana Pochampally  1 ,  David J Hamilton  5 ,  Bernd Meibohm  1 ,  Evan S Glazer  3  4 ,  Duane D Miller  1  2 ,  Wei Li  1  2  4
Affiliations
  • 1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
  • 2. College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
  • 3. Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
  • 4. Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA.
  • 5. Department of Comparative Medicine, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
PMID: 41408705 DOI: 10.1111/bph.70294
Abstract

Background and purpose: The clinical success of small-molecule drugs in treating pancreatic and prostate Cancer patients has been both promising and challenging. Whereas patients with advanced-stage tumours have significant initial responses to chemotherapy, many have experienced rapid resistance, metastasis and recurrence after curative-intent surgery. Traditional tubulin inhibitors are widely used in Cancer treatment, but their effectiveness is often limited by drug resistance and toxicity. SB-216, a novel colchicine-binding site inhibitor (CBSI), has been reported to demonstrate potential efficacy in overcoming paclitaxel (PTX) resistance in a melanoma xenograft model (A375/TxR) and inhibiting spontaneous metastasis.

Experimental approach: We evaluated SB-216 as a therapeutic option for advanced malignancies, specifically castration-resistant prostate Cancer (CRPC) and pancreatic ductal adenocarcinoma (PDAC). We conducted preclinical evaluations of SB-216 in CRPC parental and taxane-resistant lines. Additionally, we investigated the effects of SB-216 on PDAC cells, xenograft models and patient-derived models.

Key results: In vitro, SB-216 potently induces G2/M phase cell cycle arrest, inhibits cell proliferation, colony formation and cell migration in a concentration-dependent manner. In vivo, SB-216 significantly attenuates tumour growth in prostate Cancer xenograft models, overcomes PTX resistance and confers a survival benefit at a dose of 2 mg kg-1 without affecting body weight. SB-216 also inhibits the growth of PDAC xenograft tumours and the growth of patient-derived cells and organoids.

Conclusions and implications: Our findings suggest that SB-216 is a promising candidate as a new generation of anti-mitotic agents for advanced Cancer, and further exploration in combination with Other agents is warranted.

Keywords
castration‐resistant prostate cancer; cell proliferation; chemotherapy; organoids; paclitaxel resistance; pancreatic ductal adenocarcinoma; tubulin colchicine‐binding site inhibitors.
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