Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Sensitivity of Endoscopic Ultrasound and Cross-Sectional Imaging

EP: 1.Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Role of the Gastroenterologist

EP: 2.Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Patient-Derived Organoids

EP: 3.Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Organoid Collection

EP: 4.Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Success of Growing Organoids

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EP: 5.Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Sensitivity of Endoscopic Ultrasound and Cross-Sectional Imaging

EP: 6.Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Expectations for the Future

EP: 7.Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer: Ongoing Research

In this fifth episode of OncChats: Taking Organoids From Bench to Bedside Through Endoscopy in Pancreatic Cancer, Toufic A. Kachaamy, MD, of City of Hope, Madappa Kundranda, MD, PhD, of Banner MD Anderson Cancer Center, and Richard Burkhart, MD, of Johns Hopkins Medicine, review the potential advantages of using endoscopic ultrasound to enhance current molecular diagnostic techniques in pancreatic cancer.

Kundranda: With endoscopic ultrasound, biopsies, FNAs and FNBs, one of the things is even with molecular profiling. Previously, it was unheard of that we could profile tumors with just a fine needle aspiration or biopsy. Now, the field has moved with regards to that. [I just want to take] a step back, [to consider] the comment that Dr Burkhart made in terms of sometimes growing normal pancreatic tissue when you’re growing an organoid. In terms of the sensitivity of an EUS and biopsy in pancreatic cancer compared with cross-sectional imaging, would you like to elaborate on that?

Burkhart: Yeah, I think that’s a great point. The sensitivity for diagnosis has certainly been improving in parallel for multiple techniques. You’ve got CT scans and MRIs, which are becoming more and more nuanced, and they have the capacity to find smaller and smaller lesions. Although that’s wonderful, they find smaller and smaller lesions of every single type, so the diagnostic capacity of your endoscopist has become more and more important. That’s [the first point].

Number two, from a molecular diagnosis standpoint, when you think about sequencing [and] about doing pharmacotyping in the future, one of the biggest limitations is that the mutational profile of pancreas cancer is very homogeneous; it’s very bland. That means if I have a biopsy, in which, let’s say 20% of the biopsy is cancer, and the KRAS mutation that I’m looking for for molecular diagnostics is a heterogeneous mutation, then my mutant allele frequency can be as low as 10% or less. In some bioinformatics pipelines, that’s not enough to call it.

As a result, on the flip side, when we enrich that cancer associated DNA by growing an organoid, we have the capacity not only to find that KRAS mutation more easily, but also mutations that are homozygous deletions, for example. So, [for example,] CDKN2A [mutations] in pancreas cancer are easily picked up with an organoid vs your primary tumor sampling [where] you don’t really recognize that the gene has been lost, because there’s so much other normal DNA in the milieu.

Check back tomorrow for the next episode in the series.