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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Published on: December 9, 2015

Advanced Urothelial Carcinoma: Overcoming Treatment Resistance through Novel Treatment Approaches

Richard M Bambury1, Jonathan E Rosenberg

  • 1Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York, NY, USA.

Frontiers in Pharmacology
|February 8, 2013
PubMed

Insights

Novel therapies targeting signaling pathways are crucial for treating metastatic urothelial carcinoma (UC) due to chemotherapy resistance. This review explores promising targeted agents and immunotherapy strategies for improved UC treatment outcomes.

Area of Science:

  • Oncology
  • Translational Research
  • Molecular Biology

Background:

  • Metastatic urothelial carcinoma (UC) treatment relies on cisplatin chemotherapy, which is often not curative.
  • Drug resistance mechanisms in UC include efflux pumps, antioxidants, and anti-apoptotic signaling.
  • Targeting aberrant signaling pathways shows promise in various cancers.

Purpose of the Study:

  • To review novel therapeutic strategies under investigation for urothelial carcinoma.
  • To discuss the evaluation and optimization of efficacy for new UC treatments.
  • To highlight the potential of targeted therapies and immunotherapies in UC.

Main Methods:

  • Review of current literature on urothelial carcinoma signaling pathways.
  • Analysis of potential therapeutic targets including PI3K/Akt/mTOR, FGFR3, HER2, and aurora kinase.
  • Discussion of anti-angiogenic and immunotherapy approaches.

Main Results:

  • Urothelial carcinoma exhibits multiple altered signaling pathways, presenting therapeutic opportunities.
  • The PI3K/Akt/mTOR pathway is frequently activated (51% of cases) via mutations or PTEN inactivation.
  • Fibroblast growth factor receptor 3 (FGFR3) is overactive in 50-60% of UC cases, with targeted agents in development.

Conclusions:

  • Novel therapeutic approaches are urgently needed for metastatic urothelial carcinoma.
  • Targeting specific molecular pathways and employing immunotherapy represent promising strategies.
  • Further research is required to optimize the efficacy of these novel treatments in UC.
Keywords:
bladder cancerchemotherapyoncogenesresistance mechanismsurothelial cancer

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