Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model.

Aim: In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model.

Materials & Methods: We used 3beta-(N-[N',N'-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids).

Results: Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids.

Beyond the genome and proteome: targeting protein modifications in cancer.

Nearly all proteins are modified in post translational events, indeed, understanding the control and function of post translational modifications (PTMs) is arguably the 'next frontier' for cancer cell biologists. The most well understood PTMs include glycosylation, phosphorylation, ubiquitination, methylation and palmitylation. Each of these modifications has been observed to be altered in cancer, affecting key cellular pathways including signal transduction, cell membrane receptor function, and protein-protein interactions.