Tumour-Derived Cell Lines and Their Potential for Therapy Prediction in Patients with Metastatic Colorectal Cancer

Abstract

The prognosis of metastatic colorectal cancer (CRC) remains poor. Patients and physicians are in need of individual therapies and precise response predictions. We investigated the predictive capacity of primary tumour material for treatment response of metastases. Mutational landscapes of primary tumours and corresponding metastases of 10 CRC patients were compared. Cell line characteristics and chemosensitivity were investigated pairwise for primary and metastatic tumours of four patients. PDX models of one patient were treated in vivo for proof of concept. Driver mutations did not differ between primaries and metastases, while the latter accumulated additional mutations. In vitro chemosensitivity testing revealed no differences for responses to 5-FU and oxaliplatin between primary and metastatic cell lines. However, irinotecan response differed significantly: the majority of metastases-derived cell lines was less sensitive to irinotecan than their matching primary counterpart. Therapy recommendations based on these findings were compared to clinical treatment response and mostly in line with the predicted outcome. Therefore, primary tumour cell models seem to be a good tool for drug response testing and conclusion drawing for later metastases. With further data from tumour-derived cell models, such predictions could improve clinical treatment decisions, both recommending likely effective therapeutic options while excluding ineffective treatments.

Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells

“…The IC 50 of curcumin ranged from 6.69 μM to 18.49 μM. Values of 0.17 μM to 80.95 μM for 5-FU, 0.04 μM to 12.80 μM for irinotecan, and <0.01 μM to 8.72 μM for oxaliplatin were observed [ 24 , 25 , 26 , 27 , 28 ] ( Table 2 ). In general, the mean IC 50 values of irinotecan and oxaliplatin were significantly lower than that of curcumin in CRC cells, with all p -values < 0.001.…”

“…A total of 1.0–1.5 × 10 4 CRC cells per well were seeded in a 96-well plate and allowed to adhere for 24 h. Cultures were treated with 1 μM–25 μM curcumin (Sigma-Aldrich, Darmstadt, Germany, CAS: 458-37-7), 1 nM–5000 µM 5-FU, 0.1 nM–1000 µM irinotecan, and 1.3 nM–20 µM oxaliplatin (pharmacy of the University Hospital Rostock, Rostock, Germany) [ 24 ], and incubated twice for 72 h each, with a medium change in between.…”

“…These values were obtained using the method described above. In detail, the cited IC 50 values of 5-FU and irinotecan in HROC87 and HROC113 were from [ 27 ], in HROC57 from [ 28 ], and in HROC277 and HROC348 from [ 24 ]; the IC 50 of irinotecan in HROC18 was from [ 26 ] and in HROC126 from [ 24 ]; while the IC 50 of oxaliplatin in HROC57 was from [ 28 ], and in HROC277 and HROC348 from [ 24 ].…”

“… n.d.: Not determined; 1 IC 50 has been reported previously: [ 24 ] 2 , [ 25 ] 3 , [ 26 ] 4 , [ 27 ] 5 , [ 28 ] 6 , compared to the IC 50 of curcumin. …”

HROP68: A rare case of medullary pancreatic cancer—characterization and chemosensitivity of the first patient-derived cell line

“…For doubling time determination, 4 × 10 4 HROP68Tu2 cells were seeded in a coated 24-well plate and allowed to attach for 72 h. To determine the mass of the vital cells, a crystal violet assay was conducted as described previously ( 16 ). Cells were stained with 0.2% crystal violet every 24 h in quadruplicates for six consecutive days and absorption was measured at 540 nm using the plate reader Tecan Infinite (Tecan, Männedorf, Switzerland).…”