Perspectives of Cell Sensitivity/Resistance Assay in Soft Tissue Sarcomas Chemotherapy.
Timur I FetisovSofya A KhazanovaPolina A ShtompelEkaterina S TrapeznikovaVictoria Y ZinovievaValeria I MarshallAnastasia A LovengerDmitriy V RogozhinTararykova A AnastasiaBeniamin Yu BokhyanGennady A BelitskyMarianna G YakubovskayaKirill I KirsanovPublished in: International journal of molecular sciences (2023)
Treatment of highly malignant soft tissue sarcomas (STSs) requires multicomponent therapy including surgery, radiotherapy, and chemotherapy. Despite the advancements in targeted cancer therapies, cytostatic drug combinations remain the gold standard for STS chemotherapy. The lack of algorithms for personalized selection of STS chemotherapy leads to unhelpful treatment of chemoresistant tumors, causing severe side effects in patients. The goal of our study is to assess the applicability of in vitro chemosensitivity/resistance assays (CSRAs) in predicting STS chemoresistance. Primary cell cultures were obtained from 148 surgery samples using enzymatic and mechanical disaggregation. CSRA was performed using resazurin-based metabolic activity measurement in cells cultured with doxorubicin, ifosfamide, their combination and docetaxel, gemcitabine, and also their combination for 7 days. Both the clinical data of patients and the CSRA results demonstrated a higher resistance of some cancer histotypes to specific drugs and their combinations. The correlation between the CSRA results for doxorubicin and ifosfamide and clinical responses to the combination chemotherapy with these drugs was demonstrated via Spearman rank order correlation. Statistically significant differences in recurrence-free survival were also shown for the groups of patients formed, according to the CSRA results. Thus, CSRAs may help both practicing physicians to avoid harmful and useless treatment, and researchers to study new resistance markers and to develop new STS drugs.
Keyphrases
- end stage renal disease
- locally advanced
- ejection fraction
- chronic kidney disease
- newly diagnosed
- minimally invasive
- soft tissue
- primary care
- peritoneal dialysis
- prognostic factors
- papillary thyroid
- signaling pathway
- high throughput
- radiation therapy
- drug delivery
- endothelial cells
- cell therapy
- induced apoptosis
- oxidative stress
- squamous cell carcinoma
- coronary artery bypass
- endoplasmic reticulum stress
- high grade
- stem cells
- early onset
- rectal cancer
- bone marrow
- coronary artery disease
- adverse drug
- electronic health record
- squamous cell
- artificial intelligence