Personalized therapy for urothelial cancer: review of the clinical evidence
Elizabeth A Guancial1, Dipanjan Chowdhury, Jonathan E Rosenberg
1Clinical Fellow in Hematology and Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue, Smith 353, Boston, MA 02115, 617-632-3779 (telephone), 617-632-5822 (fax), eguancial@partners.org.
Abstract:
Despite a detailed understanding of the molecular aberrations driving the development of urothelial cancers, this knowledge has not translated into advances for the treatment of this disease. Urothelial cancers are chemosensitive, and platinum-based combination chemotherapy remains the standard of care for advanced disease, as well as neoadjuvant and adjuvant therapy for locally advanced disease. However, nearly half of patients who undergo resection of locally advanced urothelial cancer will relapse and eventually develop platinum-resistant disease. Clinical trials of targeted agents against angiogenesis and growth factors, as well as novel chemotheraputics, have generally been unsuccessful in urothelial cancers. Improvements in the theraputic arsenal for urothelial cancer depend upon identification of new targets and strategies to overcome platinum resistance.
Insights
Despite understanding urothelial cancer's molecular drivers, treatments remain limited. Platinum-based chemotherapy is standard, but resistance develops, necessitating new therapeutic strategies for advanced urothelial cancer.
Area of Science:
- Oncology
- Urothelial Carcinomas
- Cancer Therapeutics
Background:
- Urothelial cancers are molecularly complex, yet treatment advances lag.
- Platinum-based chemotherapy is the current standard for advanced and locally advanced urothelial cancer.
- A significant challenge is the development of platinum resistance in nearly half of patients post-resection.
Purpose of the Study:
- To highlight the unmet need for improved urothelial cancer therapies.
- To underscore the limitations of current treatment strategies, including targeted agents and novel chemotherapeutics.
- To emphasize the critical requirement for identifying new therapeutic targets and overcoming platinum resistance.
Main Methods:
- Review of current treatment paradigms for urothelial cancer.
- Analysis of the efficacy of existing and investigational therapies.
- Identification of challenges in clinical trial outcomes for urothelial cancer.
Main Results:
- Platinum-based chemotherapy remains the standard of care despite limited success in overcoming resistance.
- Clinical trials involving targeted agents and novel chemotherapeutics have shown limited efficacy.
- A substantial proportion of patients with locally advanced urothelial cancer relapse with platinum-resistant disease.
Conclusions:
- Current therapeutic strategies for urothelial cancer are insufficient, particularly in managing platinum-resistant disease.
- There is a critical need for novel therapeutic targets and strategies to improve patient outcomes.
- Overcoming platinum resistance is paramount for advancing urothelial cancer treatment.
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