A158 DEVELOPMENT OF MODELS TO SUDY THE INTERACTION BETWEEN CANCER STEM CELLS AND THE MICROENVIRONMENT IN COLON CANCER
Bibliographic record
Abstract
Abstract Background Colon cancer affects 1 in 15 people and is the 3rd deadliest cancer worldwide. The standard of care consists of surgical resection combined with 5-fluorouracil (5-FU) chemotherapy. However, relapses remain frequent due to a partial or complete loss of sensitivity to treatment, also known as chemoresistance. Over the last decades, studies have revealed the importance of intratumoral heterogeneity in this phenomenon, and in particular of two components: cancer stem cells (CSCs) and the microenvironment. CSCs are cells with a high capacity of self-renewal, potency (ability to give rise to different cell types) and resistance to anti-cancer treatments. The microenvironment, for its part, comprises all the components surrounding tumour cells, such as cancer-associated fibroblasts (CAFs). Although their respective importance in resistance has been well studied, it is important to better understand their respective modulation during resistance as well as their interactions. Aims Identify the specific changes occurring in CSCs and CAFs, as well as their interactions, during the induction of 5-FU resistance in colon cancer. Methods To achieve this goal, we are establishing 5-FU resistant models using organoid lines from colon cancer patients. First, we validated that parental organoids maintain their expected cellular heterogeneity by immunofluorescence. We also confirmed that our parental organoids are sensitive to 5-FU by measuring the survival through a WST1 assay. Results Indeed, we showed the presence of CSCs (ALDH1+) and proliferative cells (Ki67+), among others. With a baseline IC50 of 5µM, we concluded that they can be used to generate a 5-FU resistant line. In addition, our initial findings suggest that the conditioned media of CAF cultures decreases the sensitivity of parental organoids to 5-FU, emphasizing the need to study deeper the interaction between these two tumor components Conclusions In summary, our preliminary results suggest that the interaction between tumor cells and CAFs modulates the response to chemotherapy. We are currently exploring whether CSCs are particularly involved in this phenomenon. In addition, we are developing patient-derived xenograft models (PDX) sensitive or resistant to 5-FU in order to study in vivo the interactions between CAFs and CSCs. At the end, this project will provide a better understanding of the changes required for resistance, paving the way for new targeted therapies Funding Agencies Canada foundation for innovation, Canada Research Chairs
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".