Appendiceal cancer gets its own preclinical model

Appendiceal cancer (malignancies of the appendix, a small tissue pouch that is part of the gastrointestinal tract) is very rare, occurring in perhaps one or two people per 1 million per year. Prognoses are mixed, with a 5-year survival rate of 67 to 97 per cent for low-grade tumours detected early, but much lower for advanced cases that may have spread to other parts of the body.

Malignancies of the appendix, a small tissue pouch that is a part of the gastrointestinal tract, are extremely uncommon; they affect fewer than one or two people per million annually. The outlook is mixed, with a 5-year survival rate for low-grade tumours discovered early ranging from 67 to 97 per cent, but much lower for advanced cases that may have spread to other body parts. The absence of an efficient preclinical model to investigate its pathology and test new medications or therapeutic approaches has been a major obstacle for cancer researchers trying to understand appendiceal cancer and find treatments.

In a paper published in the print issue of Clinical Cancer Research, researchers at the University of California San Diego School of Medicine and Moores Cancer Center at UC San Diego Health describe the first preclinical model of appendiceal cancer that contains all elements of the tumour, allowing previously stymied investigations to proceed. "We've learned that appendiceal cancer has a distinctive genomic landscape and is surprisingly full of immune cells," said senior author Andrew Lowy, MD, chief of the Division of Surgical Oncology at Moores Cancer Center and a professor of surgery at UC San Diego School of Medicine.

"Relying on other models, such as colorectal, doesn't apply, which makes this an unmet need. Epithelial neoplasms (new, abnormal tissue growth) of the appendix are rare, but without an effective way to study them, the opportunities to develop new treatments have also been rare." The obstacles to creating a preclinical model of appendiceal cancer are numerous:

1. Access to clinical tissues is rare because the disease is rare.2. The majority of neoplasms have mucinous histology, a characteristic that makes them difficult to assess under a microscope and to culture.3. Mice do not have the equivalent of a human appendix, rendering them unsuitable as a genetically modified model. 4. Lowy and colleagues developed an organotypic slice culture of living appendiceal cancer cells. Organotypic slices are three-dimensional cultures of an organ. In this case, the slices are made from appendiceal cancer tissue removed from patients at the surgery, then cultured ex vivo, or outside, of the patient. Organotypic slices have been created to model other cancers, such as pancreatic, lung and colon, but not appendiceal, until now.

The authors said the organotypic model accurately recapitulates appendiceal tumours in terms of cell mix and behaviour, which makes it a promising new research tool in addition to other approaches, such as organoids and patient-derived xenografts (transplanted tissue grown in another species, such as a mouse or rat). "We've learned that utilizing tissue slices made from patient tumour resections is a great way to study the pathobiology of this disease, and we are hopeful they will help predict therapy responses in patients," said Lowy. "Using this new model, we can now test new treatments that might lead to better outcomes for patients with advanced disease." (ANI)

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