by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene-editing technology, the team is making significant headway in understanding and combating this deadly disease.
Ovarian cancer is notorious for its vague symptoms, which often result in delayed diagnosis. Dr. Lindsay Brubaker, a gynecologic oncologist and assistant professor at the University of Colorado School of Medicine, emphasizes the urgent need to better comprehend the drivers of progression and chemoresistance in ovarian cancer.
The most common subtype of ovarian cancer, high-grade serous carcinoma, primarily originates in the fallopian tubes rather than the ovaries. This subtype is particularly challenging to treat, as it is commonly diagnosed at an advanced stage, and the cancer often recurs. Dr. Brubaker explains that cells from the fallopian tubes detach from the epithelium and spread to other parts of the body, including the ovaries and abdominal cavity. However, the exact mechanisms and timing of this spread are still being actively researched.
In 2019, Dr. Brubaker and Dr. Benjamin Bitler, an ovarian cancer biologist, launched an ambitious genome-wide study using CRISPR/Cas9 gene-editing technology. Their objective was to identify critical drivers of the disease, particularly those that had not previously been associated with ovarian cancer. The study yielded promising results, paving the way for future experiments and providing valuable insights into the nature of this complex disease.
Building on their findings, the researchers focused on a gene called CASC4, which displayed high expression levels in ovarian cancer. Despite limited knowledge about this gene, the Bitler Lab discovered that high CASC4 expression was linked to poor clinical outcomes in high-grade serous carcinoma. Furthermore, they found that CASC4 played a pivotal role in helping cancer cells evade death during disease progression and chemotherapy treatment. These findings suggest that CASC4 could potentially serve as a biomarker for detecting early stages of ovarian cancer and improving the efficacy of chemotherapy.
In addition, the team utilized their CRISPR study results to design inhibitors that target novel cancer genes. In a study published in Expert Opinion on Therapeutic Targets, they successfully developed a peptide that blocks CBX2, a protein known to promote ovarian cancer progression and chemotherapy resistance. The peptide showed promising results in inhibiting tumor progression in both in vitro and in vivo experiments.
Looking ahead, Dr. Brubaker and her team aim to enhance the effectiveness of the peptide inhibitor, with the ultimate goal of conducting clinical trials. These projects are a direct outcome of the initial CRISPR study and highlight the tremendous potential offered by this revolutionary gene-editing technology.
Dr. Bitler acknowledges the critical role played by Dr. Brubaker’s foundational work in driving these advancements. He emphasizes the collaborative and resourceful environment at the University of Colorado Anschutz Medical Campus, which enables researchers to leverage a wide range of expertise and cutting-edge technology, such as the Functional Genomics Shared Resource.
The groundbreaking CRISPR study conducted by the University of Colorado Anschutz Medical Campus holds immense promise in the fight against ovarian cancer. By shedding light on the drivers of disease progression and developing targeted treatments, researchers are bringing us one step closer to overcoming this deadly disease.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
