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Identifying therapeutic targets by peeking inside the bladder cancer

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Identifying therapeutic targets by peeking inside the bladder cancer

Bladder cancer, which is one of the most severe forms of cancer, begins as a tumour in one of the innermost layers and spreads to the outer layers. It affects the urinary bladder, a hollow muscular organ that stores urine and excess of proteins and salts filtered by the kidneys. The lining of the bladder has layers of heterogeneous networks of cells.

Before treating cancer, doctors begin by identifying the stage of the disease. They determine the location, type and size of the tumour, and how deeply it has invaded the organ and its spread to different parts of the body. Some bladder cancers do not have a definite stage due to its diverse cellular makeup, but spread aggressively. These 'non-type' cancers progress to an advanced stage without any symptoms, and most patients realise it when it's too late. A tumour that was easy to manage becomes untreatable.

A recent study by a team of researchers from India, Singapore and France gives some insights into diagnosing bladder cancer early enough and preventing misinterpretation. The study, published in The Journal Of Clinical Medicine, was funded by the Department of Science and Technology (DST). It uses different bladder cancer cell-based models to identify proteins that lead to aggressive non-type bladder cancer.

"Most conventional forms of treating bladder cancer, for example, surgery or chemotherapy, fall short when it comes to treating a rapidly advancing bladder cancer. Due to an inefficient treatment, cancer most likely recurs, which is a common feature of bladder cancer," says Prof Prashant Kumar. He is a Faculty Scientist at the Institute of Bioinformatics, Bangalore and also the corresponding author of this study. "It is crucial to inspect the different pathways that make cancer more aggressive," he adds.

Phosphoproteins are formed when phosphate groups are attached to proteins present in the body. These modified proteins can now virtually control all metabolic activities by transmitting chemical signals throughout the cell. The current study focuses on identifying such proteins that lead to the onset of cancer. The researchers isolated these 3125 such proteins and identified two promising drug targets.

The integrin chemical pathway in a healthy cell plays a role in binding cells together by maintaining cell integrity, repairing tissues and defending against malice. The study found that unusual behaviour in this pathway helped in the progression of non-type bladder cancer. Two potential chemical messengers associated with this pathway—GSK3A/B and CDK1 proteins—were found to be modified in unusually high quantities during bladder cancer. The researchers hypothesise that inhibiting these two proteins can form a strong basis for treating bladder cancers, especially the non-type one, which is the most aggressive form of cancer.

The findings of the study throw some light on understanding the causes and effects of bladder cancer, and help in identifying novel drug targets that can also be repurposed  to treat other cancers.

"A potential future direction of our study would be to arrive at precision medicine by a similar study," concludes Dr Kumar.


This article has been run past the researchers, whose work is covered, to ensure accuracy.