Exploring Hub Genes: A New Frontier in Bladder Cancer Research
How Gene Expression Data is used by ThinkBio to Expand the Treatment Options for Bladder Cancer
Bladder cancer remains one of the most prevalent cancers worldwide, and while advancements in targeted and personalized therapies have made significant strides, there is still a pressing need for developing newer therapies that will benefit more patients.
What if the key to unlocking these breakthroughs lies in understanding the genes that act as central regulators of critical cellular processes? Our team’s latest research uncovers just that, a promising approach that could improve how bladder cancer is clinically managed!
But what are hub genes, and why are they so crucial in diseases, including cancer? In this blog post, we will take you through the science behind our findings and explain how targeting some of these pivotal genes could open new opportunities to treat bladder cancer.
What Are Hub Genes and Why Do They Matter?
In the complex web of cellular activities, genes do not function in isolation—they are part of vast networks that interact with other genes to regulate biological processes that are determinants of health and disease. Hub genes are central connectors responsible for the stability and functionality of the networks.
They ensure cellular and tissue homeostasis, and disruptions to these genes can have serious consequences, including triggering uncontrolled cell growth, a hallmark of cancer. Because of their central role, hub genes are vital not only for understanding the mechanisms of cancer but also for developing new targeted therapies that could effectively stop cancer progression in its tracks.
Leveraging the centrality of Hub Genes for developing novel therapies
Given their central role in cellular processes, hub genes offer significant potential in cancer treatment:
- Targeted Therapies: Hub genes can be targeted by drugs to cause collapse of the network and slow or halt cancer growth more effectively.
- Disease Biomarkers: When healthy tissue progresses towards a disease, we see changes in the Hub gene networks. Could these changes be used to discover disease biomarkers?
- Personalized Medicine: Genetic diversity between us is reflected in diseases. In some individuals’ diseases progress slowly, whereas in others, they are aggressive. Similarly, drugs work better in some and not in others, although the two individuals may share the same disease characteristics. Hub genes and their relationships with other genes can offer development of personalized therapies.
ThinkBio strategy: How We Leveraged Gene Expression data in this scientific journey?
We used state-of-the-art bioinformatics tools, and relied on public knowledge repositories to identify bladder cancer genes that showed higher messenger RNA expression (aka upregulated) or lower RNA expression (aka downregulated) in cancer, compared to normal bladder tissue. These genes are called differentially regulated genes (DEGs).
We then created protein networks using the DEGs to discover key hub genes enriched in cancer, and explored the biological pathways in which they are involved, including important cancer-related processes, also referred to as the “hallmarks of cancer”.
Key Findings: Pathways and Potential Drug Targets
Through this analysis, we discovered several key features about bladder cancer, some of which are well known, and a few that were novel. For example, cancer-driver pathways, RAS and PI3K/AKT were enriched in our list of features demonstrating that the analysis identified what is known and expected.
These enriched pathways discovered by this analysis have FDA approved therapies, or have investigational drugs currently under evaluation in clinical trials. These drugs, which have not been assessed for efficacy in bladder cancer are prime candidates for investigation. The network information could even be deployed for patient stratification during clinical trial design increasing their chances of success. Significantly, our analysis also identified a new pathway in bladder cancer, not previously thought to be associated with this disease indication. The Sonic Hedgehog pathway, targeted in Basal Cell Carcinoma (a type of skin cancer) has an approved drug sonidegib. Assessing the efficacy of sonidegib in a subset of bladder cancer patients, whose tumors are dependent on sonic hedgehog pathway is a key finding of our analysis.
Prognostic value of hub genes
Given that hub genes keep crucial cellular networks stable and functional it is expected that diseases will be impacted by these genes. The study tested this hypothesis and found that all the hub genes, without exception were associated with poor survival when their expression
was deregulated. Therefore, the value of these genes goes beyond drug development, into the realm of disease progression.
By focusing on these genes, doctors may be able to better assess cancer severity and tailor treatments to individual patients, ultimately improving long-term disease outcomes.
Conclusion: New Horizons for Bladder Cancer Treatment
Our study highlights the potential of hub genes as both prognostic and therapeutic assets in bladder cancer. By understanding the role in cancer progression, we are moving closer to developing more precise, effective treatments that are tailored to the individual molecular profile of each patient’s cancer.
For those interested in the full details of our research methodology and findings, we invite you to read our original research paper, which delves deeper into the data and analysis that led to these promising conclusions.