Tissue obtained from tumors during an autopsy conducted shortly after a cancer patient’s death provides unique insights into how the tumors evolved, spread and resisted treatment. The Frederick National Laboratory’s Molecular Characterization Laboratory reports on results of a study on preclinical models established from “rapid autopsy” tumors during the 2020 American Society for Clinical Oncology Virtual Scientific Program, May 29-31.

Lindsay Dutko in the Molecular Characterization Laboratory's histology group.
Lindsay Dutko in the Molecular Characterization Laboratory's histology group.

The Molecular Characterization Laboratory team studied specimens from the National Cancer Institute’s Patient-Derived Models Repository, which houses preclinical mouse models as well as cell lines and three-dimensional cell cultures known as “organoids” derived from patient tumors. A subset is derived from rapid autopsy specimens. The laboratory analyzed tumor specimens from pancreatic cancer patients and included cells and organoids from the original tumor and specimens from organs where the cancer had spread, such as the liver, colon and lung.

Genomic analysis of the tumors showed the key gene mutations that drove the cancer in the first place and were present in both the original tumor and in all of the tissues where it spread. However, the genome of each metastasized tumor was different from the primary tumor and from other metastases in unique ways.

The data demonstrated how the rapid autopsy models provide a distinct resource for preclinical studies about the original tumor and tumors in the organs where the cancer spread.

Analyzing a tumor tissue obtained at autopsy provides the opportunity to determine what caused the cancer to spread and why it stopped responding to treatment.

The Molecular Characterization Laboratory team conducted tumor genomic analysis and served as authors on two additional studies in the ASCO program. A phase 1 trial evaluated the efficacy of a Wee1 kinase inhibitor in patients with ovarian and endometrial cancer.

The team has played a key role in the launch and ongoing operation of NCI-MATCH, a multiple-arm clinical trial which enrolls patients with cancer in studies of targeted therapies based on a corresponding gene mutation specifically targeted by the therapy.

NCI-MATCH investigators will have an oral presentation of results of a phase 2 study of the investigational treatment copanlisib among patients whose tumors harbored mutations in the PIK3CA gene.