A quick peek into some of the promising studies from around the world on breast cancer diagnostics and therapeutics from last week.
In vitro and in vivo studies by Singh et al published in Nanomedicine have shown that covalently linked glucosamine and non-covalently phospholipids- glucosamine coated carbon nanotubes called glycol- MWCNTs have preferential accumulation in breast tumor tissue through a specific interaction with glucose receptors. This is promising in developing more accurate diagnostic tools as well as improved targeted therapy by molecular radiotherapy.
An interesting study from China by Jun Yan et al showed that 1ml suspension of carbon nanoparticles when injected into the body had excellent tissue retention specifically in axillary lymph nodes. Hence, it can be used 10-15 minutes before surgery to exclusively target axillary lymphnodes for sentinel node biopsy and dissection. The tissue targeting and identification rate is proven to be significantly higher than conventional blue dye.
Tumor Infiltrating Lymphocytes (TILs) have always been an enigma for cancer biologists. A review by Ahn et al on the subject throws light on the increased prognostic evidence and predictive potential of TILs in triple negative and Her2 positive breast cancers.
Deregulation of TET1 and 3 under hypoxia in tumor tissue is of high prognostic value in tumor progression and aggressiveness. Belmonte et al studied the DNA hydroxymethylation associated with these genes during hypoxia to effectively explain the downstream mediation of p38-MAPK pathway in breast tumors with poor outcome.
In silico analyses have opened up new insights into the binding and downstream signaling contribution of Protease activated receptor 2 (PAR2). Though specific ligand binding sights have not been explored, putative ligand specific conformations of PAR 2 are analyzed more in this study by Kakarala et al. It is quite interesting to note that there is a bias in the binding of PAR 2 to different receptors and this gives agonistic action with serotonin type 1, β adrenergic type 1 and antagonistic action with substance K (NK1), serotonin type 2, thromboxane and dopamine type 4 receptors.
Poly-ADP-ribose polymerase (PARP) mediated signaling pathways play significant role in breast cancer cells that PARP inhibition to silence homologous recombination is a hot topic in developing new therapeutic agents. But the sensitivity of cancer cells especially in TNBC is not sufficient enough to propagate this idea further. Wiegmans et al’s study from the Signal Transduction Laboratory in Queensland have shown positive results that if combined with histone deacetylase inhibitors like SAHA and ROMI, with PARPinhibitors, effective HR pathway silencing mediated by RAD51, BARD1, and FANCD2 takes place. Optimistic for adjuvant therapy in breast cancer especially TNBC.
This is giving the preliminary basis towards a more rational drug design in metastasizing breast tumors.