Mutated DNA Repair Genes Offer Worse Prognosis
New research suggests a link between some DNA repair genes and the ability to predict prognosis of patients with bladder and other related cancers.
In their study, Dr. Monika Joshi and colleagues found that bladder cancer patients with mutations in their ATM or RB1 genes tended not to live as long as their counterparts. In their role as researchers, they are trying to find biomarkers that will help understand the differences between patients and their prognoses, and to develop better therapies.
“We’re coming to realize that not every cancer patient is the same,” Joshi said. “We see some patients responding to therapies, while others do not. Treatments like chemotherapy and immunotherapy, do not have a 100 per cent response rate. So we’re trying to delve deeper to better understand biological differences between patients.”
Mutations in DNA repair genes, such as ATM and RB1, play a significant role in tumour growth and how cancer responds to treatment. As a result, mutations in these types of genes are often found in patients with bladder cancer. Previous research has already demonstrated a connection between these mutations and who respond better to certain types of chemotherapy.
“These genes help repair damage to the DNA, but when these genes are mutated, they actually reduce the repair response, allowing tumour cells with defective DNA to proliferate,” Joshi said. “And when those tumour cells are proliferating, at that point they may be more susceptible to certain treatments like chemotherapy.”
The predictive value of ATM and RB1 genes was analysed using two separate data sets; 130 bladder cancer patients logged in the Cancer Genome Atlas, and 81 bladder (and related) cancer patients from three academic medical centres.
Mutations in the ATM or RB1 genes were found in nearly a quarter of both data sets, with patients having a shorter than average prognosis. The results of the analysis were published in Oncotarget back in March.
“If we know patients with this gene have a poorer prognosis, we can focus our efforts to learn more about why this might be happening so we can improve therapies for these patients,” Joshi said. “We might not have all the answers after this study, but I think it helps pave the way for future development of targeted therapies in bladder cancer.”
Ming Yin, Monali Vasekar and Joseph J. Drabick, all of the Penn State Cancer Institute; Petros Grivas, University of Washington; Hamid Emamekhoo, University of Wisconsin Carbone Cancer Center; Prateek Mendiratta, Cleveland Clinic Taussig Center Institute; Siraj Ali, Foundation Medicine; JoAnn Hsu, City of Hope Comprehensive Cancer Center; and Sumanta Pal, City of Hope Comprehensive Cancer Center, also participated in this research.
This study received no specific funding.