An overview on precision therapy in bladder cancer

ABSTRACT

Introduction

Bladder cancer is a common global cause of morbidity and mortality, with many patients not responding to -or not tolerating- traditional chemotherapeutic regimens. Recent studies have allowed us to utilize the genetic profile of tumors to better target therapy as is required, as well as innovate novel therapeutic interventions usable when more traditional options prove futile.

Areas covered

The development of novel interventions in bladder cancer, particularly immune checkpoint inhibitors, as well as using genetic markers to guide both traditional and novel therapeutic interventions. We also discuss the utility of these markers in diagnosing and prognosticating bladder cancer patients.

Expert opinion

Biomarker-guided therapy could revolutionize bladder cancer care in several ways: not only do novel therapeutic agents provide alternate treatment options for more difficult cases, but it can also increase the efficacy of more traditional treatment options. In addition, it may have a role in the early diagnosis and detection of bladder cancer, as well as predicting the course and prognosis of these patients. Unresolved challenges include how to best optimize therapy with novel agents as regarding duration and patient selection, as well as investigations as to whether using gene-guidance results in clinically improved patient outcomes.

KEYWORDS:

• Biomarker
• bladder Cancer
• drug Therapy
• immunotherapy
• neoadjuvant chemotherapy
• target therapy
• precision medicine

Article highlights

• Mutations in ARID1A and TP53 as well as expression of Ezrin are useful in predicting patient prognosis after BCG therapy. However, further studies are needed to establish their usefulness as clinical screening tools by which to guide therapy.

• Mutations associated with both the nucleotide repair pathway (ERCC2) and the homologous repair pathway (ATM, RB1, FANCC) are valuable potential indicators for patient response to cisplatin neoadjuvant therapy.

• ERBB2 mutations have also been identified in cisplatin responders and should be further evaluated for their clinical value.

• ctDNA is practical and has shown great promise in predicting both patient response and prognosis. It has the potential to replace downstaging as the evaluation method of choice; however, it needs to be further evaluated in order to ensure its efficacy amongst the heterogenous bladder cancer population.

• Monoclonal antibodies targeting the growth factor receptors FGFR, EGFR, Her2/Neu, and VEGF are perhaps the most practical approach towards the future of personalized medicine in bladder cancer therapy.

• Immunomodulators such as mTOR inhibitors, and AKT inhibitors show potential in the treatment of bladder cancer.

• PDL-1 expression, in combination with other markers, can potentially predict patient response to PDL-1 inhibitors, maximising the drug’s therapeutic potential.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Ethics approval and consent to participate

The study was approved by the ASU-Faculty of Medicine ethical committee.

Consent for publication

All authors have read the manuscript and agree to all its contents. All authors give their consent for publication.

Availability of data and material

Not applicable.

Author contribution

Ahmed Sayed & Malak Munir have equally contributed to the paper in planning, conducting, analyzing, writing the manuscript, and modifying it in response to reviewers comments. Noor Eweis shared in data collection and writing the manuscript. Other coauthors shared in data collection. Sanaa Eissa has revised and submitted the manuscript.

Additional information

Funding

This paper was not funded.