Introduction: Bladder cancer is a significant global health burden, ranking as the ninth most common
cancer worldwide. In 2020, there were approximately 573,000 new cases of bladder cancer
and 213,000 deaths globally. The high incidence and mortality rates of bladder cancer
.underscore the need for effective therapeutic strategies to combat this disease
Survivin is a member of the inhibitor of apoptosis (IAP) family and plays a crucial role in
inhibiting cell death and regulating cell division. It is selectively overexpressed in many types
of cancer, including bladder cancer, and is associated with poor prognosis and increased
tumor aggressiveness
Overall, survivin is a promising target for bladder cancer therapy due to its significant role in.
tumor growth and resistance to apoptosis. Targeting survivin through various strategies,
including siRNA and combination therapies, holds potential for improving bladder cancer
treatment outcomes
Methods: A systematic search was made in four major databases: PubMed, Web of Science, SID, and
Magiran. Searches were made for the period from 1999 to 2024; the keywords used
included "bladder cancer" AND "survivin." The Boolean operator "AND" has been applied in
retrieval to ensure that only those studies which discuss both bladder cancer and survivin
have been traced. In the database SID, a total of two relevant studies were found. The
search within PubMed initially retrieved 319 articles. After the application of these criteria, 20
articles were selected for detailed analysis. In an attempt to refine the selection, the following
inclusion criteria were applied: relevance of the study to bladder cancer and survivin,
adequacy of data volume, and a focus on the biological or clinical aspects of survivin in
bladder cancer. Using these criteria,. Web of Science and Magiran were also searched. By
eliminating duplicate studies and using the inclusion criteria, a total number of 34 articles
were included to be deeply reviewed
Results: The expression of survivin in bladder cancer involves several mechanisms and pathways
Stabilization by FAT10: FAT10, a ubiquitin-like protein, is upregulated in bladder cancer and
binds to survivin, preventing its ubiquitin-mediated degradation. This stabilization of survivin
promotes cancer cell proliferation Regulation by Specificity Protein (Sp) Transcription Factors: Curcumin, a polyphenolic
compound, has been shown to decrease survivin expression by down-regulating Sp1, Sp3,
and Sp4 transcription factors. These Sp proteins are crucial for the expression of survivin
and other genes involved in cell survival and angiogenesis
.
Interaction with CDC2 Kinase and MAPK/AKT Pathways: Baicalein, a bioactive flavonoid,
reduces survivin expression and induces apoptosis in bladder cancer cells. This process
involves the inhibition of CDC2 kinase and modulation of the p38 MAPK and AKT pathways,
which regulate survivin levels and cell cycle progression
.
Role of AATF: The apoptosis antagonizing transcription factor (AATF) is overexpressed in
bladder cancer and upregulates survivin expression. AATF enhances cell proliferation and
decreases sensitivity to chemotherapy by increasing survivin levels
.
Spliced Variants: Survivin has several spliced variants, such as survivin-deltaEx3 and
survivin-2B, which have different roles in tumor progression. High expression of survivin and
survivin-deltaEx3 is associated with higher tumor grades and poor prognosis, while
survivin-2B is inversely correlated with tumor grade
.
These mechanisms highlight the complex regulation of survivin in bladder cancer and its
potential as a therapeutic target
Conclusion: Strengths:
* Prognostic Marker: Multiple studies confirm survivin's role as a prognostic marker, providing valuable information for patient management [Jeon, 2013].
* Therapeutic Target: Effective down-regulation of survivin through siRNA and combination therapies shows promise in reducing tumor growth and enhancing apoptosis [Hou, 2006] [Wang, 2014].
* Diagnostic Tool: Urine survivin offers a non-invasive, accurate diagnostic method, improving early detection and monitoring [Shariat, 2004] [El-Hakim, 2014].
Weaknesses:
* Heterogeneity: Variability in study designs, patient populations, and detection methods can lead to inconsistent results and interpretations [Jeon, 2013].
* Polymorphism Impact: The influence of survivin polymorphisms on cancer risk and progression requires further validation in larger, diverse cohorts [Kawata, 2011].
* Clinical Translation: While preclinical results are promising, translating survivin-targeted therapies into clinical practice remains challenging due to potential off-target effects and delivery issues [Hou, 2006].
However, the current research on survivin is not without its limitations. One major challenge is the heterogeneity among studies, including variations in study designs, patient populations, and detection methods, which can lead to inconsistent results and complicate the interpretation of findings. Additionally, the impact of survivin polymorphisms on cancer risk and progression, although promising, requires further validation in larger and more diverse cohorts to ensure broader applicability.
Furthermore, the translation of survivin-targeted therapies from preclinical studies to clinical practice remains a significant hurdle. Despite promising results in laboratory settings, challenges such as potential off-target effects and issues related to the delivery of survivin inhibitors must be addressed before these therapies can be widely adopted in clinical settings.
In summary, while survivin holds substantial promise as a multifaceted protein with significant implications for bladder cancer, further well-designed studies are essential. These studies should aim to standardize assays, validate findings across diverse populations, and address the challenges associated with clinical translation to fully realize the potential of survivin in cancer diagnosis, prognosis, and therapy.