Among the various types of cancer, Urothelial Bladder Cancer (UBC) is responsible for around 2 lakh deaths per year around the world. This cancer affects the inner lining of the bladder and is the most common form of bladder cancer. It usually affects aged individuals, with blood in urine and painful urination as the first sign of its manifestation. Conventional methods of treatment involve surgical removal of cancerous tissue in the bladder and chemotherapy. However, they do not prevent the recurrence of UBC.
In a recent study, a team of researchers from the Institute of Bioinformatics, Bengaluru, Manipal Academy of Higher Education (MAHE), Manipal, Med Genome Labs Ltd., Bengaluru, and Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, have studied urothelial bladder cancer in a 19-year old individual to improvise possible treatment options. The study, published in the journal Frontiers in Oncology, was funded by the Department of Biotechnology (DBT) and the Department of Science and Technology (DST). The researchers were particularly interested in investigating the genetic mutations that result in urothelial bladder cancer in an young adult.
The 19-year old boy they studied had no previous family history of cancer.
"Our study aimed to find if UBC follows a similar trend as seen with the aged, or if it follows a different path in young adults. If different, we wanted to know how," says Prof. Prashant Kumar, Faculty Scientist at the Institute of Bioinformatics, Bengaluru. His research team included Dr. Jyoti Sharma, Barnali Deb and Irene A. George. “Our study might bea starting point for others to follow," he adds.
The researchers identified somatic mutations—mutations that occur in all the cells of the body except reproductive cells—using an advanced gene sequencing technique.The researchers isolated DNA from tumour and blood samples of the patient and subjected them to a process called whole-exome sequencing. This method allows the sequencing of all exomes—portions of the DNA coding for a particular protein. These exomes harbour majority of genetic mutations, which may result in advanced and metastatic progression of cancer.
"The study was highly challenging especially in obtaining the patient's sample and keeping track of follow-up onthe survival was a difficult task to achieve," shares Prof Prashant.
The study found mutations in potential 'driver genes' like TP53, along with those involved in ion channel transportation. Driver genes are genes that drive a cell to undergo unregulated cell divisions, and ion channels allow selective passage of ions necessary for body functions. The researchers predicted that among all mutations, there are eight with the likelihood of driving the cells towards cancerous growth. Interestingly, they also found mutations in a gene called RB1, which is associated with the death of the individual with UBC. Further analysis revealed mutations in 18 genes, which take part in activities of ion-channels.
Many studies in the past have shown the role of ion channels in the development of cancer. However, few have identified them as an anti-cancer therapeutic target. The inhibition of certain types of ion channels helps treat breast and pancreatic cancer. While in others, like lung cancer, prostate cancer and melanoma, blocking these ion channels stops cell multiplication. Therefore, obstructing ion channels like calcium and sodium-potassium could be promising drug designing options against UBC, as these channels regulate the growth and multiplication of cells.
While UBC is known to occur commonly among individuals in their sunset years, affecting a young individual without any family history is an unusual phenomenon. This study attempts to investigate the reasons and highlight novel therapeutic target against UBC.
This article has been run past the researchers, whose work is covered, to ensure accuracy.