Cell membrane modulation as adjuvant in cancer therapy

Abstract

Cancer is a complex disease involving numerous biological processes, which can exist in parallel, can be complementary, or are engaged when needed and as such can replace each other. This redundancy in possibilities cancer cells have, are fundamental to failure of therapy. However, intrinsic features of tumor cells and tumors as a whole provide also opportunities for therapy. Here we discuss the unique and specific makeup and arrangement of cell membranes of tumor cells and how these may help treatment. Interestingly, knowledge on cell membranes and associated structures is present already for decades, while application of membrane modification and manipulation as part of cancer therapy is lagging. Recent developments of scientific tools concerning lipids and lipid metabolism, opened new and previously unknown aspects of tumor cells and indicate possible differences in lipid composition and membrane function of tumor cells compared to healthy cells. This field, coined Lipidomics, demonstrates the importance of lipid components in cell membrane in several illnesses. Important alterations in cancer, and specially in resistant cancer cells compared to normal cells, opened the door to new therapeutic strategies. Moreover, the ability to modulate membrane components and/or properties has become a reality. Here, developments in cancer-related Lipidomics and strategies to interfere specifically with cancer cell membranes and how these affect cancer treatment are discussed. We hypothesize that combination of lipid or membrane targeted strategies with available care to improve chemotherapy, radiotherapy and immunotherapy will bring the much needed change in treatment in the years to come.

Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents

“…3b). These changes can be triggered by various stimuli, including genetic mutations, abnormal epigenetic modifications, and carcinogenic substances [23, 233–236]. If allowed to operate unchecked, the resulting loss of homeostasis can lead to reprogramming of vital cellular features such as plasma membrane order and nanoclustering (Fig.…”

Decreased Efficacy of Doxorubicin Corresponds With Modifications in Lipid Metabolism Markers and Fatty Acid Profiles in Breast Tumors From Obese vs. Lean Mice

“…Both SFAs and MUFAs are implicated in alterations within cancer cell membrane composition known as membrane lipid saturation. These FA classes are more resistant to lipid peroxidation, which in turn protects cancerous cells against oxidative stress induced by therapies (11,12). The role of omega-6 (n-6) PUFAs in breast cancer development, progression as well as treatment resistance, includes n-6 PUFAs exhibiting pro-inflammatory effects mediated by lipid-derived bioactive mediators i.e., eicosanoids, prostaglandins and leukotrienes (13,14).…”

The dental calculus metabolome in modern and historic samples

“…They play roles in 514 local (intracellular) (Nishizuka 1995) and long-distance (hormone) cell signaling (Xavier et 515 al. 2016), have both pro-and anti-inflammatory properties (Bennett and Gilroy 2016), and 516 are the major components of cell membranes, where their composition influences cell 517 membrane function (Zalba and Hagen 2017). Bacterial membrane lipid content varies by 518 species (López-Lara and Geiger 2016), and may indicate bacterial physiological status 519 (Darveau et al 2004), while pathogenesis of the periodontal disease-associated oral 520…”