State-of-the-art microscopy techniques for the imaging of living cells
Therapy resistance is a major problem in cancer treatment. Despite pharma’s major efforts to develop new targeted therapies, there is still poor understanding at the cellular level to what extent targeted drugs effectuate complete and uniform pathway inhibition in human tumors. Patient-derived tumor organoids recapitulate the histopathological features of native tumors, including patient specific responses towards therapies. Moreover, organoids develop cellular heterogeneities in respect to cell fate and signaling activities, providing a platform to study single-cell drug responses towards targeted inhibitors in the context of population dynamics and therapy resistance. To understand functional heterogeneities between cells in colorectal cancers (CRC), I will discuss recent developments regarding quantitative measurements of signaling activity in drug-challenged patient-derived CRC organoids in real-time and at single-cell resolution. In parallel, we established live-monitoring of evolving tumor cell genomes to reveal the intrinsic instability of tumor genomes and the wide diversity of karyotypes that are being generated in tumors that are ultimately subjected to selection for malignant fitness.
Together, capturing single-cell behavior in tumor organoids provide great potential to unravel cellular heterogeneity that underlies resistance mechanisms.
About Dr. Hugo Snippert
Dr. Hugo Snippert is Group Leader at the department of Molecular Cancer Research within the Center of Molecular Medicine at the University Medical Center Utrecht. Hugo received his PhD (cum laude) in the lab of Hans Clevers (Hubrecht Institute). He initiated his own research line in the MCR department of the UMC Utrecht to understand heterogeneity in (stem) cell behavior during tumor formation and cancer progression. In 2016, he became group leader in the MCR department, where his group exploits the unique combination of I) primary human cancer samples (tumor organoids), II) molecular genetics to engineer and manipulate human cancers and III) real-time imaging to monitor and quantify cellular behavior to study phenotypic heterogeneity between cancer cells, with the long term goal to understand and prevent therapy resistance in cancer.