Since their first discovery in the 1960s by Alec Bangham, liposomes have been shown to be effective drug delivery systems for treating various cancers. Several liposome-based formulations received approval by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), with many others in clinical trials. Liposomes have several advantages, including improved pharmacokinetic properties of the encapsulated drug, reduced systemic toxicity, extended circulation time, and targeted disposition in tumor sites due to the enhanced permeability and retention (EPR) mechanism. However, it is worth noting that despite their efficacy in treating various cancers, liposomes still have some potential toxicity and lack specific targeting and disposition. This explains, in part, why their translation into the clinic has progressed only incrementally, which poses the need for more research to focus on addressing such translational limitations. This review summarizes the main properties of liposomes, their current status in cancer therapy, and their limitations and challenges to achieving maximal therapeutic efficacy.

Protein post-translational modifications (PTMs) in eukaryotic cells play important roles in the regulation of functionalities of the proteome and in the tempo-spatial control of cellular processes. Most PTMs enact their regulatory functions by affecting the biochemical properties of substrate proteins such as altering structural conformation, protein–protein interaction, and protein–nucleic acid interaction. Amid various PTMs, arginine methylation is widespread in all eukaryotic organisms, from yeasts to humans. Arginine methylation in many situations can drastically or subtly affect the interactions of substrate proteins with their partnering proteins or nucleic acids, thus impacting major cellular programs. Recently, arginine methylation has become an important regulator of the formation of membrane-less organelles inside cells, a phenomenon of liquid–liquid phase separation (LLPS), through altering π-cation interactions. Another unique feature of arginine methylation lies in its impact on cellular physiology through its downstream amino acid product, asymmetric dimethylarginine (ADMA). Accumulation of ADMA in cells and in the circulating bloodstream is connected with endothelial dysfunction and a variety of syndromes of cardiovascular diseases. Herein, we review the current knowledge and understanding of protein arginine methylation in regards to its canonical function in direct protein regulation, as well as the biological axis of protein arginine methylation and ADMA biology.

Emergence of androgen-independent cancer cells during androgen deprivation therapy presents a significant challenge to successful treatment outcomes in prostate cancer. Elucidating the role of androgen deprivation in the transition from an androgen-dependent to an androgen-independent state may enable the development of more effective therapeutic strategies against prostate cancer. Herein, we describe an in vitro model for assessing the effects of continuous androgen-deprivation on prostate cancer cells (LNCaP) with respect to the expression of two prostate-specific markers: the androgen receptor (AR) and prostate-specific membrane antigen (PSMA). Compared with androgen-containing normal growth medium, androgen-deprived medium apparently induced the concomitant downregulation of AR and PSMA over time. Decreased protein levels were confirmed by fluorescence imaging, western blotting and enzymatic activity studies. In contrast to the current understanding of AR and PSMA in prostate cancer progression, our data demonstrated that androgen-deprivation induced a decrease in AR and PSMA levels in androgen-sensitive LNCaP cells, which may be associated with the development of more aggressive disease-state following androgen deprivation therapy.

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of cancers, making PRMTs potential therapeutic targets. But it remains not well understood how PRMTs impact specific oncogenic pathways. We previously identified PRMTs as important regulators of cell growth in neuroblastoma, a deadly childhood tumor of the sympathetic nervous system. Here, we demonstrate a critical role for PRMT1 in neuroblastoma cell survival. PRMT1 depletion decreased the ability of murine neuroblastoma sphere cells to grow and form spheres, and suppressed proliferation and induced apoptosis of human neuroblastoma cells. Mechanistic studies reveal the prosurvival factor, activating transcription factor 5 (ATF5) as a downstream effector of PRMT1-mediated survival signaling. Furthermore, a diamidine class of PRMT1 inhibitors exhibited anti-neuroblastoma efficacy both in vitro and in vivo. Importantly, overexpression of ATF5 rescued cell apoptosis triggered by PRMT1 inhibition genetically or pharmacologically. Taken together, our findings shed new insights into PRMT1 signaling pathway, and provide evidence for PRMT1 as an actionable therapeutic target in neuroblastoma.