scholarly journals Mechanistic science in cardiovascular-oncology: the way forward to maximise anti-cancer drug effects and minimise cardiovascular toxicity

2021 ◽  
Vol 135 (23) ◽  
pp. 2661-2663
Author(s):  
Ninian N. Lang ◽  
Rhian M. Touyz
Keyword(s):  
Cardiovascular Health ◽  
Cancer Survival ◽  
Rapid Development ◽  
Drug Effects ◽  
Minimum Cost ◽  
Cardiovascular Effects ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Cardiovascular Toxicity ◽  
Anti Cancer

Abstract Dramatic improvements in cancer survival have arisen because of the rapid development of novel anti-cancer therapies. The potential for cardiovascular toxicity associated with these drugs often reflects overlap between pathogenic cancer mechanisms and physiological pathways required for normal cardiovascular function. Clinical Science has, therefore, compiled a themed collection on Cardiovascular-Oncology. This collection examines the intersection between cancer treatments and their potentially harmful cardiovascular effects. By defining the mechanisms underlying unwanted cardiovascular effects of anti-cancer therapies, cardioprotective strategies can be developed. Only by doing so, will patients be able to achieve optimal cancer treatment at the minimum cost to cardiovascular health.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

Cancer therapy-related cardiac dysfunction: is endothelial dysfunction at the heart of the matter?

2021 ◽  
Vol 135 (12) ◽  
pp. 1487-1503
Author(s):  
Crizza Ching ◽  
Dakota Gustafson ◽  
Paaladinesh Thavendiranathan ◽  
Jason E. Fish
Keyword(s):  
Cancer Therapy ◽  
Cardiac Dysfunction ◽  
Inflammatory Markers ◽  
Cancer Survival ◽  
Growth Factor Receptor ◽  
Cardiovascular Effects ◽  
Cardiovascular Complications ◽  
Cardiac Biomarkers ◽  
Cancer Therapies ◽  
The Impact

Abstract Significant improvements in cancer survival have brought to light unintended long-term adverse cardiovascular effects associated with cancer treatment. Although capable of manifesting a broad range of cardiovascular complications, cancer therapy-related cardiac dysfunction (CTRCD) remains particularly common among the mainstay anthracycline-based and human epidermal growth factor receptor-targeted therapies. Unfortunately, the early asymptomatic stages of CTRCD are difficult to detect by cardiac imaging alone, and the initiating mechanisms remain incompletely understood. More recently, circulating inflammatory markers, cardiac biomarkers, microRNAs, and extracellular vesicles (EVs) have been considered as early markers of cardiovascular injury. Concomitantly, the role of the endothelium in regulating cardiac function in the context of CTRCD is starting to be understood. In this review, we highlight the impact of breast cancer therapies on the cardiovascular system with a focus on the endothelium, and examine the status of circulating biomarkers, including inflammatory markers, cardiac biomarkers, microRNAs, and endothelial cell-derived EVs. Investigation of these emerging biomarkers may uncover mechanisms of injury, detect early stages of cardiovascular damage, and elucidate novel therapeutic approaches.

A Review of the Cardiovascular Effects of Oncology Agents

2008 ◽  
Vol 21 (2) ◽  
pp. 146-158 ◽  
Author(s):  
Bradi L. Frei ◽  
Scott A. Soefje
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Adverse Effect ◽  
Cancer Therapy ◽  
Cardiovascular Effects ◽  
Cancer Therapies ◽  
Cardiovascular Toxicity ◽  
Action Monitoring ◽  
Increased Risk ◽  
Chemotherapy Agents

Cardiovascular toxicity is an important adverse effect of several classes of oncology drugs. Because cancer survivors are living longer, the late effects of cancer therapy must be addressed. Many patients diagnosed with cancer are already at an increased risk for cardiovascular disease before drug treatment. Select chemotherapy agents further complicate the issue because of their own ability to induce cardiovascular toxicities or exacerbate preexisting conditions. Hypertension, dyslipidemia, heart failure, and arrhythmia are known consequences of some cancer therapies. This review provides an overview of the epidemiology, mechanism of action, monitoring, and management of these cardiovascular effects.

Polymer Modification Of An Anti-Cancer Drug: Effects Of Hydrophilization

2005 ◽  
Vol 9 (1) ◽  
pp. 13-14 ◽  
Author(s):  
Jung-Sun Sohn ◽  
Soo-Kyung Choi ◽  
Byung-Wook Jo ◽  
Michael Hess
Keyword(s):  
Drug Effects ◽  
Cancer Drug ◽  
Polymer Modification ◽  
Anti Cancer

scholarly journals An in vitro quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopenias

2019 ◽  
Author(s):  
Jennifer L. Wilson ◽  
Dan Lu ◽  
Nick Corr ◽  
Aaron Fullerton ◽  
James Lu
Keyword(s):  
Blood Cell ◽  
Drug Effects ◽  
Cell Killing ◽  
Cancer Therapies ◽  
Systems Pharmacology ◽  
Drug Induced ◽  
Quantitative Systems Pharmacology ◽  
Cell Lineages ◽  
Anti Cancer

AbstractMyelosuppression is one of the most common and severe adverse events associated with anti-cancer therapies and can be a source of drug attrition. Current mathematical modeling methods for assessing cytopenia risk rely on indirect measurements of drug effects and primarily focus on single lineage responses to drugs. However, anti-cancer therapies have diverse mechanisms with varying degrees of effect across hematopoietic lineages. To improve predictive understanding of drug-induced myelosuppression, we developed a quantitative systems pharmacology (QSP) model of hematopoiesis in vitro for quantifying the effects of anti-cancer agents on multiple hematopoietic cell lineages. We calibrated the system parameters of the model to cell kinetics data without treatment and then validated the model by showing that the inferred mechanisms of anti-proliferation and/or cell-killing are consistent with the published mechanisms for three classes of drugs with different mechanisms of action. Using a set of compounds as a sample set, we then analyzed novel compounds to predict their mechanisms and magnitude of myelosuppression. Further, these quantitative mechanisms are valuable for the development of translational in vivo models to predict clinical cytopenia effects.Author SummaryReduced bone marrow activity and levels of mature blood cells is an undesirable side effect of many anti-cancer therapies. Selecting promising lead compounds for further development requires understanding of potential myelosuppressive effects. However, existing preclinical experiments and modeling formulations fail to consider drug effects on multiple blood cell types or the mechanistic differences between how drugs induced myelosuppression. Here we developed a quantitative systems pharmacology (QSP) model that estimates a drug candidate’s effect on multiple precursor and mature blood cell lineages and further distinguishes how the drug affects these populations - through cell-killing or anti-proliferation mechanisms. This modeling formalism is valuable for vetting compounds for therapeutic development and for further translational modeling to anticipate the clinical effects of compounds.

scholarly journals Data of a fluorescent imaging-based analysis of anti-cancer drug effects on three-dimensional cultures of breast cancer cells

Data in Brief ◽  
2015 ◽  
Vol 5 ◽  
pp. 429-433 ◽  
Author(s):  
Junji Itou ◽  
Sunao Tanaka ◽  
Wenzhao Li ◽  
Yoshiaki Matsumoto ◽  
Fumiaki Sato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Drug Effects ◽  
Fluorescent Imaging ◽  
Cancer Drug ◽  
Anti Cancer

scholarly journals Structure-Based Classification and Anti-Cancer Effects of Plant Metabolites

2018 ◽  
Vol 19 (9) ◽  
pp. 2651 ◽  
Author(s):  
Seong-Ah Shin ◽  
Sun Young Moon ◽  
Woe-Yeon Kim ◽  
Seung-Mann Paek ◽  
Hyun Ho Park ◽  
...  
Keyword(s):  
Side Effects ◽  
Drug Development ◽  
Human Population ◽  
Negative Impact ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Plant Metabolites ◽  
Current State ◽  
Anti Cancer ◽  
Further Development

variety of malignant cancers affect the global human population. Although a wide variety of approaches to cancer treatment have been studied and used clinically (surgery, radiotherapy, chemotherapy, and immunotherapy), the toxic side effects of cancer therapies have a negative impact on patients and impede progress in conquering cancer. Plant metabolites are emerging as new leads for anti-cancer drug development. This review summarizes these plant metabolites with regard to their structures and the types of cancer against which they show activity, organized by the organ or tissues in which each cancer forms. This information will be helpful for understanding the current state of knowledge of the anti-cancer effects of various plant metabolites against major types of cancer for the further development of novel anti-cancer drugs.

scholarly journals Two Targets, One Hit: new Anticancer Therapeutics to Prevent Tumorigenesis Without Cardiotoxicity

2021 ◽  
Vol 11 ◽  
Author(s):  
Zoltán Szabó ◽  
Lilla Hornyák ◽  
Márton Miskei ◽  
Lóránt Székvölgyi
Keyword(s):  
Adverse Effect ◽  
Cell Proliferation ◽  
Antineoplastic Agents ◽  
Cancer Therapeutics ◽  
Therapeutic Interventions ◽  
Cancer Therapies ◽  
Cancer Cell Proliferation ◽  
Cardiovascular Toxicity ◽  
Allosteric Inhibitors ◽  
Anti Cancer

A serious adverse effect of cancer therapies is cardiovascular toxicity, which significantly limits the widespread use of antineoplastic agents. The promising new field of cardio-oncology offers the identification of potent anti-cancer therapeutics that effectively inhibit cancer cell proliferation without causing cardiotoxicity. Future introduction of recently identified cardio-safe compounds into clinical practice (including ERK dimerization inhibitors or BAX allosteric inhibitors) is expected to help oncologists avoid unwanted cardiological complications associated with therapeutic interventions.

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