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The Pivotal Role of Lipids in Cancer Pathophysiology, Diagnosis and Therapy

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 9807

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Special Issue Editors

Prof. Dr. Jacinta Serpa

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Guest Editor

NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria 130, 1169-056 Lisboa, Portugal
Interests: cancer metabolism; tumor microenvironment; mechanisms of therapy resistance; metabolic remodeling; metabolism-based therapies; oxidative stress; metabolic players; metabolic targets

Dr. Cindy Mendes

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Guest Editor

NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria 130, 1169-056 Lisboa, Portugal
Interests: cancer metabolism; tumor microenvironment; metabolic reprogramming; metabolism-based therapies; therapy resistance; cellular bioenergetics; cell signaling

Special Issue Information

Dear Colleagues,

Lipids are important players in all the intercrossed points of cellular endogenous metabolism. In addition to valuable metabolic sources for biosynthesis and bioenergetics, lipids are important regulators of cell and system function. Therefore, the entire molecular network that goes from lipid bioavailability (transport, synthesis and degradation circuitries) to their function is relevant in cancer. This Special Issue is dedicated to the relevance of lipids in cancer pathophysiology, considering their versatile use as disease markers for diagnosis, prognosis and follow up. Moreover, the identification of their metabolic and signaling pathways as suitable therapeutic targets to fight cancer is also of notice. All the researchers who are dedicated to studying the fundamental role of lipids in cancer and the development of new diagnostic and therapeutic lipid-based strategies are invited to submit scientific papers to be considered for publication in the scope of the Cancers’ Special Issue The Pivotal Role of Lipids in Cancer Pathophysiology, Diagnosis and Therapy.

Prof. Dr. Jacinta Serpa
Dr. Cindy Mendes
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

lipid biogenesis
lipid circuitries in cancer
lipid transport
regulation of lipid bioavailability
lipid turnover
cancer features dependent on lipids
novel diagnosis and prognosis tools
new therapies

Published Papers (4 papers)

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Research

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15 pages, 2772 KiB

Open AccessArticle

Modulation of Plasma Lipidomic Profiles in Metastatic Castration-Resistant Prostate Cancer by Simvastatin

by Blossom Mak, Hui-Ming Lin, Thy Duong, Kate L. Mahon, Anthony M. Joshua, Martin R. Stockler, Howard Gurney, Francis Parnis, Alison Zhang, Tahlia Scheinberg, Gary Wittert, Lisa M. Butler, David Sullivan, Andrew J. Hoy, Peter J. Meikle and Lisa G. Horvath

Cancers 2022, 14(19), 4792; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194792 - 30 Sep 2022

Cited by 5 | Viewed by 1624

Abstract

Elevated circulating sphingolipids are associated with shorter overall survival and therapeutic resistance in metastatic castration-resistant prostate cancer (mCRPC), suggesting that perturbations in sphingolipid metabolism promotes prostate cancer growth. This study assessed whether addition of simvastatin to standard treatment for mCRPC can modify a poor prognostic circulating lipidomic profile represented by a validated 3-lipid signature (3LS). Men with mCRPC (n = 27) who were not on a lipid-lowering agent, were given simvastatin for 12 weeks (40 mg orally, once daily) with commencement of standard treatment. Lipidomic profiling was performed on their plasma sampled at baseline and after 12 weeks of treatment. Only 11 men had the poor prognostic 3LS at baseline, of whom five (45%) did not retain the 3LS after simvastatin treatment (expected conversion rate with standard treatment = 19%). At baseline, the plasma profiles of men with the 3LS displayed higher levels (p < 0.05) of sphingolipids (ceramides, hexosylceramides and sphingomyelins) than those of men without the 3LS. These plasma sphingolipids were reduced after statin treatment in men who lost the 3LS (mean decrease: 23–52%, p < 0.05), but not in men with persistent 3LS, and were independent of changes to plasma cholesterol, LDL-C or triacylglycerol. In conclusion, simvastatin in addition to standard treatment can modify the poor prognostic circulating lipidomic profile in mCRPC into a more favourable profile at twice the expected conversion rate. Full article

(This article belongs to the Special Issue The Pivotal Role of Lipids in Cancer Pathophysiology, Diagnosis and Therapy)

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18 pages, 3692 KiB

Open AccessArticle

Lipid Status of A2780 Ovarian Cancer Cells after Treatment with Ruthenium Complex Modified with Carbon Dot Nanocarriers: A Multimodal SR-FTIR Spectroscopy and MALDI TOF Mass Spectrometry Study

by Maja D. Nešić, Tanja Dučić, Manuel Algarra, Iva Popović, Milutin Stepić, Mara Gonçalves and Marijana Petković

Cancers 2022, 14(5), 1182; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051182 - 24 Feb 2022

Cited by 6 | Viewed by 2190

Abstract

In the last decade, targeting membrane lipids in cancer cells has been a promising approach that deserves attention in the field of anticancer drug development. To get a comprehensive understanding of the effect of the drug [Ru(η⁵-Cp)(PPh₃)₂CN] (RuCN) on cell lipidic components, we combine complementary analytical approaches, matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI TOF MS) and synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy. Techniques are used for screening the effect of potential metallodrug, RuCN, without and with drug carriers (carbon dots (CDs) and nitrogen-doped carbon dots (N-CDs)) on the lipids of the human ovarian cancer cell line A2780. MALDI TOF MS results revealed that the lysis of ovarian cancer membrane lipids is promoted by RuCN and not by drug carriers (CDs and N-CDs). Furthermore, SR-FTIR results strongly suggested that the phospholipids of cancer cells undergo oxidative stress after the treatment with RuCN that was accompanied by the disordering of the fatty acid chains. On the other hand, using (N-)CDs as RuCN nanocarriers prevented the oxidative stress caused by RuCN but did not prevent the disordering of the fatty acid chain packing. Finally, we demonstrated that RuCN and RuCN/(N-)CDs alter the hydration of the membrane surface in the membrane–water interface region. Full article

(This article belongs to the Special Issue The Pivotal Role of Lipids in Cancer Pathophysiology, Diagnosis and Therapy)

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19 pages, 5873 KiB

Open AccessArticle

¹H-NMR Plasma Lipoproteins Profile Analysis Reveals Lipid Metabolism Alterations in HER2-Positive Breast Cancer Patients

by Giuseppe Corona, Emanuela Di Gregorio, Alessia Vignoli, Elena Muraro, Agostino Steffan and Gianmaria Miolo

Cancers 2021, 13(22), 5845; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225845 - 21 Nov 2021

Cited by 6 | Viewed by 2301

Abstract

The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward ¹H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins’ fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline ¹H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients’ group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of ¹H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies. Full article

(This article belongs to the Special Issue The Pivotal Role of Lipids in Cancer Pathophysiology, Diagnosis and Therapy)

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Review

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17 pages, 1902 KiB

Open AccessReview

PCSK9 Inhibitors in Cancer Patients Treated with Immune-Checkpoint Inhibitors to Reduce Cardiovascular Events: New Frontiers in Cardioncology

by Vincenzo Quagliariello, Irma Bisceglia, Massimiliano Berretta, Martina Iovine, Maria Laura Canale, Carlo Maurea, Vienna Giordano, Andrea Paccone, Alessandro Inno and Nicola Maurea

Cancers 2023, 15(5), 1397; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051397 - 22 Feb 2023

Cited by 11 | Viewed by 2911

Abstract

Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts. Moreover, PCSK9 induces peripheral immune tolerance (inhibition of cancer cell- immune recognition), reduces cardiac mitochondrial metabolism, and enhances cancer cell survival. The present review summarizes the potential benefits of PCSK9 inhibition through selective blocking antibodies and siRNA in patients with cancer, especially in those treated with ICIs therapies, in order to reduce atherosclerotic cardiovascular events and potentially improve ICIs-related anticancer functions. Full article

(This article belongs to the Special Issue The Pivotal Role of Lipids in Cancer Pathophysiology, Diagnosis and Therapy)

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