Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies

Wit, Sanne de; Glen, Claire; Boer, Rudolf A. de; Lang, Ninian N.

doi:10.1093/cvr/cvac132

Cited by 21 publications

(20 citation statements)

References 270 publications

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“…To better understand the results presented in Belzutifan inhibits hypoxia-inducible factor 2α (HIF-2α), and research suggests that HIF-2α inhibitors can reverse pulmonary hypertension and that there are shared pathophysiologic mechanisms between cancer and heart failure [24,25] . Carvedilol, a nonselective beta-adrenergic antagonist, has anti-free radical and antioxidant effects, and can resist oxidation and reduce ROS production [26] .…”

Section: The Mid Embeddings Can Represent the Cell Phenotypesmentioning

confidence: 99%

More Is Different: Drug Property Analysis on Cellular High-Content Images Using Deep Learning

Gao¹,

Guo²,

Zhang³

et al. 2023

Preprint

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High-content analysis (HCA) holds enormous potential for drug discovery and research, but widely used methods can be cumbersome and yield inaccurate results. Noise and high similarity in cell images impede the accuracy of deep learning-based image analysis. To address these issues, we introduce More Is Different (MID), a novel HCA method that combines cellular experiments, image processing, and deep learning modeling. MID effectively combines the convolutional neural network and Transformer to encode high-content images, effectively filtering out noisy signals and characterizing cell phenotypes with high precision. In comparative tests on drug-induced cardiotoxicity and mitochondrial toxicity classification, as well as compound classification, MID outperformed both DeepProfiler and CellProfiler, which are two highly recognized methods in HCA. We believe that our results demonstrate the utility and versatility of MID and anticipate its widespread adoption in HCA for advancing drug development and disease research.

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Section: The Mid Embeddings Can Represent the Cell Phenotypesmentioning

confidence: 99%

More Is Different: Drug Property Analysis on Cellular High-Content Images Using Deep Learning

Gao¹,

Guo²,

Zhang³

et al. 2023

Preprint

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“…Recently, it has become clear that HF and cancer share several pathophysiological characteristics and often coincide in the same patient. 1 , 2 Although most attention has gone out to cancer patients with incident cardiovascular disease (CVD) (cardio-oncology), more awareness is given to the increased prevalence of cancer in HF patients (reverse cardio-oncology), including colorectal cancer (CRC)), reported by several independent cohorts recently. 3–5 In the last few years, several pre-clinical studies have provided mechanistic evidence that HF can stimulate tumour growth.…”

Section: Introductionmentioning

confidence: 99%

Heart failure-induced microbial dysbiosis contributes to colonic tumour formation in mice

de Wit,

Geerlings,

Shi

et al. 2024

Cardiovascular Research

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Introduction Heart failure (HF) and cancer are the leading causes of death worldwide. Epidemiological studies revealed that HF patients are prone to develop cancer. Preclinical studies provided some insights into this connection, but the exact mechanisms remain elusive. In colorectal cancer (CRC), gut microbial dysbiosis is linked to cancer progression and recent studies have shown that HF patients display microbial dysbiosis. Aim This current study focussed on the effects of HF-induced microbial dysbiosis on colonic tumour formation. Methods and Results C57BL/6J mice were subjected to myocardial infarction (MI), with sham surgery as control. After six weeks faeces were collected, processed for 16s rRNA sequencing, and pooled for faecal microbiota transplantation. CRC tumour growth was provoked in germ-free mice by treating them with Azoxymethane/Dextran sodium sulphate. The CRC mice were transplanted with faeces from MI or sham mice. MI-induced HF resulted in microbial dysbiosis, characterized by a decreased α-diversity and microbial alterations on the genus level, several of which have been associated with CRC. We then performed, faecal microbiota transplantation with faeces from HF mice in CRC mice, which resulted in a higher endoscopic disease score and an increase in the number of tumours in CRC mice. Conclusion We demonstrated that MI-induced HF contributes to colonic tumour formation by altering the gut microbiota composition, providing a mechanistic explanation for the observed association between HF and increased risk for cancer. Targeting the microbiome may present as a tool to mitigate HF-associated co-morbidities, especially cancer.

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“… 6 Furthermore, inflammatory cytokines and metabolic aberrations in glucose oxidation, aerobic glycolysis, and de novo lipogenesis have been implicated in the connection between HF and cancer. 8 , 9 Clonal haematopoiesis of undetermined significance due to somatic mutations and abnormal fibroblast proliferation are all shared characteristics between cancer and CVD. 8–10 …”

Section: Introductionmentioning

confidence: 99%

Association between heart failure and the incidence of cancer: a systematic review and meta-analysis

Jaiswal

Ang

Agrawal

et al. 2023

European Heart Journal Open

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Background The association between heart failure (HF) patients and the incidence of cancer is not well understood, with conflicting results to date. Objective The aim of this meta-analysis was to evaluate whether patients with HF have a higher risk of developing cancer. Material and Methods We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10th December 2022. Primary clinical outcomes were the incidence of cancer. Secondary endpoints were the incidence of breast cancer, lung cancer, hematological cancer, colorectal cancer, and prostate cancer. Results A total of 10 articles with 7,335,834 (518,105 Heart Failure vs. 6,817,729 non-Heart Failure) patients were involved in the analysis. The mean age of the patients with HF and the non-HF group was 70.0 and 69.2 years. The median follow-up duration was 5.1 years. The most common Comorbidity among both groups includes DM (27.67% vs. 14.53%) and HTN (81.88% vs. 57.5%). Patients with HF were associated with a significant increase in the incidence of cancer, [HR, 1.43 (95%CI: 1.22-1.68), P<0.001], breast cancer [HR, 1.28 (95%CI: 1.09-1.50), P<0.00], lung cancer [HR, 1.89 (95%CI: 1.25-2.85), P<0.001), hematological cancer [HR, 1.63 (95%CI: 1.15-2.33), P=0.01), colorectal cancer [HR, 1.32 (95%CI: 1.11-1.57), P<0.001) compared with patients without HF. However, the incidence of prostate cancer was comparable between both groups [HR, 0.97 (95%CI: 0.66-1.43), p=0.88]. Conclusion This meta-analysis confirms that the state of heart failure is associated with a higher risk for incident cancer. These data may aid in raising awareness with physicians that cancer may develop in patients with prevalent heart failure and that early screening and evaluation may be useful in an early diagnosis of cancer.

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Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies

Cited by 21 publications

References 270 publications

More Is Different: Drug Property Analysis on Cellular High-Content Images Using Deep Learning

More Is Different: Drug Property Analysis on Cellular High-Content Images Using Deep Learning

Heart failure-induced microbial dysbiosis contributes to colonic tumour formation in mice

Association between heart failure and the incidence of cancer: a systematic review and meta-analysis

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