Emerging strategies for the improvement of chemotherapy in bladder cancer: Current knowledge and future perspectives
Sen Liu1, Xu Chen2, Tianxin Lin2
1Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Background:
Chemotherapy is a first-line treatment for advanced and metastatic bladder cancer, but the unsatisfactory objective response rate to this treatment yields poor 5-year patient survival. Only PD-1/PD-L1-based immune checkpoint inhibitors, FGFR3 inhibitors and antibody-drug conjugates are approved by the FDA to be used in bladder cancer, mainly for platinum-refractory or platinum-ineligible locally advanced or metastatic urothelial carcinoma. Emerging studies indicate that the combination of targeted therapy and chemotherapy shows better efficacy than targeted therapy or chemotherapy alone. Newly identified targets in cancer cells and various functions of the tumour microenvironment have spawned novel agents and regimens, which give impetus to sensitizing chemotherapy in the bladder cancer setting.
Aim Of Review:
This review aims to present the current evidence for potentiating the efficacy of chemotherapy in bladder cancer. We focus on combining chemotherapy with other treatments as follows: targeted therapy, including immunotherapy and antibody-drug conjugates in clinic; novel targeted drugs and nanoparticles in preclinical models and potential targets that may contribute to chemosensitivity in future clinical practice. The prospect of precision therapy is also discussed in bladder cancer.
Key Scientific Concepts Of Review:
Combining chemotherapy drugs with immune checkpoint inhibitors, antibody-drug conjugates and VEGF inhibitors potentially elevates the response rate and survival. Novel targets, including cancer stem cells, DNA damage repair, antiapoptosis, drug metabolism and the tumour microenvironment, contribute to chemosensitization. Gene alteration-based drug selection and patient-derived xenograft- and organoid-based drug validation are the future for precision therapy.
Insights
Combining chemotherapy with targeted therapies like immune checkpoint inhibitors and antibody-drug conjugates can improve outcomes for advanced bladder cancer patients. Novel targets and precision medicine approaches are key to enhancing chemotherapy effectiveness.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Chemotherapy is a primary treatment for advanced bladder cancer, but its effectiveness is limited, leading to poor survival rates.
- Current approved treatments include immune checkpoint inhibitors, FGFR3 inhibitors, and antibody-drug conjugates, primarily for platinum-refractory or ineligible patients.
- Emerging research suggests combining chemotherapy with targeted therapies enhances efficacy compared to monotherapy.
Purpose of the Study:
- To review current evidence on potentiating chemotherapy efficacy in bladder cancer.
- To focus on combining chemotherapy with targeted therapies, including immunotherapy and antibody-drug conjugates.
- To explore novel targeted drugs, nanoparticles, and potential chemosensitizing targets for future clinical application.
Main Methods:
- Review of existing clinical evidence and preclinical studies.
- Analysis of novel targeted agents and their mechanisms.
- Discussion of emerging targets and precision medicine strategies in bladder cancer.
Main Results:
- Combining chemotherapy with immune checkpoint inhibitors, antibody-drug conjugates, and VEGF inhibitors may improve response rates and survival.
- Novel targets such as cancer stem cells, DNA damage repair pathways, and the tumor microenvironment are identified as crucial for chemosensitization.
- Gene alteration-based drug selection and patient-derived models are highlighted as future directions for precision therapy.
Conclusions:
- Combination therapies offer a promising strategy to enhance chemotherapy effectiveness in bladder cancer.
- Understanding novel targets and the tumor microenvironment is vital for developing more effective treatments.
- Precision medicine, guided by genetic profiling and advanced validation models, represents the future of bladder cancer treatment.
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