Nuclear assembly as a target for anti-cancer therapies

Abstract

Current anti-cancer therapies have a great deal of undesirable side effects; therefore, there is a need to develop efficient and cancer cell-specific new drugs without strong dose-limiting side effects. In my opinion, mechanisms of nuclear assembly and organization represent a novel platform for drug targets, which might fulfill these criteria. The nuclear stiffness and organization of some cancer types are often compromised, making them more vulnerable for further targeting the mechanisms of nuclear integrity than their normal counterparts. Here I will discuss the nuclear organization of normal cells and cancer cells, the molecular mechanisms that govern nuclear assembly with emphasis on those that, in my view, might be considered as targets for future anti-cancer therapies.

Ursolic acid exerts anti-cancer activity by suppressing vaccinia-related kinase 1-mediated damage repair in lung cancer cells

“…Defects in VRK1 cause abnormal nuclear envelope structure, likely due to altered BAF function 62 . This suggests that VRK1 is an attractive target in the treatment of cancer, as cancer cells have abnormally fragile nuclear structure and are susceptible to killing under conditions that disturb nuclear envelope dynamics 63 . We have tested this by employing small molecule VRK1 inhibitors that inhibit the VRK1-mediated BAF phosphorylation and consequently prevent nuclear envelope break down or reassembly in cancer cells, suggesting that inhibition of VRK1 renders cancer cells, which contain underlying nuclear envelope defects, more vulnerable 64 65 .…”

Characterization of increasing stages of invasiveness identifies stromal/cancer cell crosstalk in rat models of mesothelioma

“…Among the proteins concerned by the most significant positive Log2FC values shared by F5-T1 and M5-T1, two nuclear proteins appear: BAF and HNRPM. The barrier-to-autointegration factor (BAF) plays a crucial role in chromatin organization, and its frequent overexpression in cancers now represents a target for therapy [ 36 , 37 ]. HNRPM is a member of the family of heterogeneous nuclear ribonucleoproteins, which was initially described as a regulator of splicing [ 38 ].…”

Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation

“…Recent discoveries of targeted molecular therapies have greatly advanced our understanding of human cancer treatments (Ghosh et al, 2014;Gorjanacz, 2014). In addition, a better comprehension of oncogene families such as musculoaponeurotic fibrosarcoma (MAF) has aroused the interests of scientists for additional research into their roles in human disease.…”