In a study recently published in Cancer Research, a journal of the American Association for Cancer Research, a team of researchers led by C. Patrick Reynolds, M.D., Ph.D., director for the Texas Tech University Health Sciences Center (TTUHSC) School of Medicine Cancer Center, sought to expand upon his lab’s previous research that showed ALT tumors identified by a biomarker known as C-circles share a common biology that confers vulnerabilities to be exploited for cancer therapy. The paper is titled, “Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function.”

Reynolds and his team of collaborators, all affiliated with the TTUHSC School of Medicine Cancer Center, included Shawn Macha, Balakrishna Koneru, Trevor A. Burrow, Charles Zhu, Dzmitry Savitski, Rakhshanda L. Rahman, M.D., Catherine A. Ronaghan, M.D., Jonas Nance, Kristyn McCoy and Cody Eslinger. The Cancer Prevention & Research Institute of Texas, the National Cancer Institute and Alex’s Lemonade Stand Foundation funded the project.

A subset of cancers exist that produce predominantly poor outcomes because their cells employ a mechanism known as alternative lengthening of telomeres (ALT) to maintain telomere length so they can continue to grow and multiply. Telomeres are caps on the end of chromosomes that serve as protectors for the genetic information contained within the cell.

To continue growing and multiplying, cancer cells must maintain their telomeres using telomere maintenance mechanisms (TMM). Without TMM, telomeres begin to erode and the cancer cell dies. The most common TMM uses a cell enzyme known as telomerase that has the ability to add DNA to the ends of chromosomes.

However, some cancer cells are able to grow continuously without turning on telomerase. Instead, they grow by using an alternate lengthening of telomeres (ALT) mechanism that can repair telomeres without telomerase. The presence of ALT has been found to be extensive in high-risk neuroblastoma and certain sarcomas, and ALT cancers are a major clinical challenge that lack targeted therapeutic approaches.

To conduct their study, the Reynolds team employed the C-circle assay to evaluate a variety of childhood and adult cancers. They found ALT positivity in pediatric cancers (neuroblastoma and sarcoma) and in adult cancers (breast, colon and lung cancers). The frequency of ALT ranged from 10% to 78%, depending on the type of cancer.

Source: Read Full Article