New Study Reveals That Muscle Invasive Bladder Cancer Cells Can Become More Susceptible To Chemotherapy

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Academic Journal
Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 30 Jun 2011 - 14:00 PDT


Sensitized muscle invasive bladder cancer cells can be eliminated by the lethal effects of chemotherapy. This has been discovered in research conducted at the UC Davis Cancer Center that was published on June 28 in the International Journal of Cancer. The current study has also strengthened the belief that microRNA (short ribonucleic molecules) play significant roles in many deadliest types of cancer.

The scientists reported that an increased production of microRNA (encoded for by the gene miR-34a) in bladder cancer cell lines resulted in a higher number of cancer cells being eliminated by cisplatin, a chemotherapy drug commonly used to treat cancer.

Ralph deVere White, UC Davis Cancer Center director and professor of urology, said:

"When we took the bladder cancer cell lines and activated miR-34a, they were more responsive to chemotherapy."

The current study is the first of its kind that has helped to establish a link between the sensitivity of bladder cancer cells to chemotherapy and the expression of the gene miR-34a. The authors suggest there might be a possible therapy that could either target the gene miR-34a for over-expression or for use as a predictor of response to chemotherapy.

At present, the survival rate five years post-diagnosis, for patients with advanced bladder cancer is about 50%. Although many studies conducted previously have provided evidence that survival rates can improve if surgery is preceded by chemotherapy, this rarely translates into clinical practice, as only less than 50% of patients respond positively. Physicians hesitate to use this as a treatment option as many patients can suffer significant adverse events without receiving any benefit at all.

deVere White said:

"So, now we have to prove that it works to predict
chemotherapy response in patients".

To achieve this UC Davis has partnered with Rosetta Genomics, an Israel based company to develop a microRNA profile that may be used to predict response to chemotherapy in patients with muscle-invasive bladder cancer.

In the current study the researchers analyzed data from 27 patients and stated that many who did not respond to the combined chemotherapy and surgery treatment were expressing low levels of the gene miR-34a. Additional research in this area is needed, the authors pointed out, as the finding was not statistically significant with p>0.05.

Expression of miR-34a before and after chemotherapy was compared by the researchers after collection of tumor samples from eight patients who did not respond to chemotherapy. Only two out of the eight patients showed some degree of increased miR-34a expression, confirming a possible relationship between low gene expression and failure to respond to chemotherapy.

deVere White said:

"We wanted to see, if you looked at the patient's tissue before chemotherapy, were there differentially expressed microRNAs in the patients who responded to the drugs versus those that didn't respond."

The authors said:

"The combined data indicate that the elevation of miR-34a expression levels prior to chemotherapy would be of benefit to muscle-invasive bladder cancer patients, particularly in a setting of low mi-R-34a expression."

MicroRNAs were discovered in 1993 by Victor Ambros, Rosalind Lee and Rhonda Feinbaum during a study of the gene lin-14 in C. elegans development. There is clear and compelling evidence of the involvement of microRNAs in a number of types of cancer. In 2007, miR-125b, a gene that encodes for microRNA was identified that causes prostate cancer to become fatal. deVere White was part of this research team.

The microRNA studied here was also recently found to play a role in medulloblastoma, an aggressive type of brain cancer. MicroRNAs, which are normally 22 to 33 nucleotides in length, are known as post-transcriptional regulators. That means they work by turning genes on or off during the part of the protein synthesis process that involves making a strand of RNA from a DNA template. The human genome encodes for an estimated 1,000 microRNAs.

The scientists stated that miR-34a will be tested for its ability to increase sensitivity to chemotherapy in future studies. More studies to analyze the expression of this gene in patients with muscle-invasive bladder cancer will also be the focus of research in future.

The researchers write: With the currently low chemotherapy success rate and poor five-year survival rate for patients with this disease, "such studies are clearly warranted."

deVere White predicted:

"If we can prove what is causing chemotherapy resistance in patients with muscle-invasive bladder cancer, American ingenuity will come up with ways to overcome it."

Ruth Vinall, Alexandra Z. Ripoll, Sisi Wang and Chong-xian Pan; are additional authors of the report and were with UC Davis at the time of the study. Source: UC Davis Cancer Center

Written by Barry Windsor
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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