The following is a summary of “Clonal evolution of long-term expanding head and neck cancer organoid: Impact on treatment response for personalized therapeutic screening,” published in the November 2023 issue of Oncology by Choi, et al.
In biobanking that uses patient-derived organoids (PDO), organoid lines must stay genetically stable so that PDO can be used in the clinic with original cancer. However, there needs to be more information on the different types of mutations and clonal development in PDO and how they affect how well a treatment works. For a study, researchers sought to find out if head and neck cancer organoids (HNCOs) could keep the genetic traits of their original tumors and understand how clones change over time, so they did target sequencing on 377 cancer-related genes and used a sub-clonal fraction model with them.
They used two HNCO lines to make dose-response curves for drugs and radiation to look at how the treatment response changed between an early passage (>passage 6) and a late passage (>passage 6). Using a 3D ex vivo organoid culture procedure, they could grow 27 HNCOs from 39 patients, giving them a 70% success rate total (27/39). Their mutational traits were very similar. Three of the HNCOs looked at showed more than 70% similarity. One HNCO was the only one with less than 50% agreement.
However, many of these organoid lines changed into clones during repeated passaging. Major cancer driver genes and VAF distributions were the same between early and later passages. Also, they discovered that all late passages of HNCOs were more sensitive to radiation than early passages. It was similar to what they saw with drugs. They report the creation of HNCO lines from 27 patients and show that their genes are identical to those found in their parent tumors. They also showed how the mutational profiles of HNCO change over time with long passage culture and how these clonal evolutions affect how well radiotherapy works.
Source: sciencedirect.com/science/article/abs/pii/S1368837523002671
