研究摘要
The integrated project proposed on exploring a novel circulating tumor cell-based approach for personalized oncology for cancers from neural crest origin. Also we are developing novel microfluidic devices for rapid analysis of cellular behavior from patient-derived cancer cells.
During the first quarter of the project, we have recruited 3 patients (a total of 18 up to now) and prepared expanded circulating tumor cells from these patients. These samples have been analyzed for the drug sensitivity profile and immunophenotyping. The clinical treatment outcome 3 months after drug treatment has been shown to correlate with CTC sensitivity profile. Also we have kicked off one clinical trial focusing on TRK fusion positive pediatric tumors (including neuroblastoma). The manuscript for one of the microfluidic devices (Digi-SACA, the automated CTC counting device) have been accepted for publication in Sensors and Actuators B. Two mamuscripts based on research done in subprojects #1 and #3 have been prepared and will be submitted during the second quarter.
With regards to each project, the research progress is on schedule. For project #1, we successfully identified STAT3-driven cancer stemness determines homing capability of breast cancer cells MCF7 and MDAMD231 to the floating alginate hydrogel, which depends on stiffness and surface porosity of the hydrogel composition. Also cell lines from small cell lung cancers are being tested in the same system and compare to breast cancer cells on its homing capability. For project#2, automated counting of PDL1+ circulating tumor cells with Digi-SACA and automated platform is done for 3 patient samples. Also IDO1 activity assay based on rare cells is being planned. For project#3, surface marker-based characterization of EMT phenotype indicated that SCLC cells are highly enriched in EMT phenotype, which may correlate to its aggressive metastatic and drug resistance behavior. For project#4, a case with recurrent neuroblastoma who failed alectinib treatment was found to have CTC cells that are refractory to alectinib with eSelect technology before the patient initiated the treatment. This is an encouraging signal for our system to be used as a tool to drive personalized oncology decision in the setting of rare diseases.
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