Nina Sanford, MD, and Wen Jiang, MD, PhD

Developing a Biochip to Personalize Treatment for Anal Cancer

Nina Sanford, MD, and Wen Jiang, MD, PhD, are working to establish a highly sensitive biomarker for anal cancer to better tailor treatment for patients based on whether their tumor is likely to respond to chemoradiation. Currently, most patients with locally advanced anal cancer are treated with definitive chemoradiation and then monitored to determine whether surgery is also needed for patients who do not respond to treatment. This is generally a one-size-fits-all plan. While ongoing trials are assessing the role of treatment intensification and de-intensification, treatment decisions remain based upon the clinical stage at diagnosis, although similarly staged anal cancer can respond differently to treatment. Dr. Sanford and Dr. Jiang aim to develop a “liquid biopsy” to dynamically measure treatment response in anal cancer, which would be an important breakthrough and could help identify those patients who need surgery sooner or who could potentially receive less or more intense chemoradiation.

The research team has developed a novel biochip technology that captures extracellular vesicles (EVs), which are membrane-bound particles secreted by all cells, including cancer cells, from a blood sample. The captured EVs contain exosomal RNAs that can be used to detect whether there maybe remnant anal cancer cells. “Our tethered lipoplex nanoparticle (TLN) assay contains molecular beacons for a specific RNA target and is easier to use and more sensitive than any existing ‘liquid biopsy’ technique,” says Dr. Jiang.

Dr. Sanford, Dr. Jiang and their teams at the University of Texas Southwestern Medical Center and MD Anderson Cancer Center respectively are:

• Developing a more sensitive immune-tethered lipoplex nanoparticle (ILN) biochip to detect anal cancer by adding antibodies against epidermal growth factor receptor (EGFR) to a biochip containing molecular beacons for microRNA-21 (miR-21). Levels of both miR-21 and EGFR have been shown to be elevated in anal cancer.
• Conducting a prospective observational study to evaluate whether the new assay can be used to monitor anal cancer during and after treatment.
• Generating predictive models of anal cancer recurrence based on miR-21 expression level and other clinical variables.

“Incidence and mortality are rising for anal cancer, and there is no well-established biomarker of treatment response,” says Dr. Sanford. “Our ILN biochip could facilitate the personalization of treatment for the growing number of patients with anal cancer and help improve their quality of life, outcomes and survival.”

Publications
 

• Age Associated Disparity in Phagocytic Clearance Affects the Efficacy of Cancer Nanotherapeutics was published on September 18, 2023 in Nature Nanotechnology.