Losartan Alleviates the Side Effects and Maintains the Anticancer Activity of Axitinib

Fu, Ying; Saxu, Rengui; Ridwan, Kadir Ahmad; Yao, Jiaping; Chen, Xiaoxuan; Xu, Xueping; Zheng, Weida; Yu, Peng; Teng, Yuou

doi:10.3390/molecules27092764

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…Recent 2022 publication demonstrated in animal models (Wistar rats) treated with Axitinib that losartan, an established angiotensin-receptor blocker, can be used to effectively reduce hypertensive effects without effect on antitumor activity. 68 A 2022 publication by Ren et al 69 found that in patients with metastatic CRC with bevacizumab-related hypertension, treatment with renin-angiotensin inhibitors showed significant survival benefits over patients treated with calcium channel blockers or no treatment. Interestingly Mice studies using lisinopril further demonstrated a positive synergistic antitumor effect with increased 5-fluorouracil tissue penetration and decrease both collagen and hyaluronic acid deposition whilst significantly downregulating the expression of TGF (transforming growth factor)-β1 and downstream SMAD (Small Mothers Against Decapentaplegic) signaling which may also improve antitumor effect.…”

Section: Vascular Endothelial Growth Factor Inhibitorsmentioning

confidence: 99%

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

et al. 2023

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Cardiovascular disease and cancer are 2 of the leading causes of death worldwide. Although improvements in outcomes have been noted for both disease entities, the success of cancer therapies has come at the cost of at times very impactful adverse events such as cardiovascular events. Hypertension has been noted as both, a side effect as well as a risk factor for the cardiotoxicity of cancer therapies. Some of these dynamics are in keeping with the role of hypertension as a cardiovascular risk factor not only for heart failure, but also for the development of coronary and cerebrovascular disease, and kidney disease and its association with a higher morbidity and mortality overall. Other aspects such as the molecular mechanisms underlying the amplification of acute and long-term cardiotoxicity risk of anthracyclines and increase in blood pressure with various cancer therapeutics remain to be elucidated. In this review, we cover the latest clinical data regarding the risk of hypertension across a spectrum of novel anticancer therapies as well as the underlying known or postulated pathophysiological mechanisms. Furthermore, we review the acute and long-term implications for the amplification of the development of cardiotoxicity with drugs not commonly associated with hypertension such as anthracyclines. An outline of management strategies, including pharmacological and lifestyle interventions as well as models of care aimed to facilitate early detection and more timely management of hypertension in patients with cancer and survivors concludes this review, which overall aims to improve both cardiovascular and cancer-specific outcomes.

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Section: Vascular Endothelial Growth Factor Inhibitorsmentioning

confidence: 99%

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

et al. 2023

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“…For these reasons, the side effects of Axitinib, a VEGFR inhibitor, occur in over 30% of patients and include diarrhea, hypertension, fatigue, loss of appetite, nausea, decreased kidney function, and anemia [ 90 , 91 ]. Since VEGFR is involved in the continuous renewal of capillaries, the blocking of these receptors could prevent the physiological repair of traumatized capillaries, facilitating the onset of bleeding.…”

Section: Side Effects and Resistance Phenomena Of Current Kismentioning

confidence: 99%

Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management

Filippone

Mannino

Casili

et al. 2022

IJMS

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High-grade brain tumors are malignant tumors with poor survival and remain the most difficult tumors to treat. An important contributing factor to the development and progression of brain tumors is their ability to evade the immune system. Several immunotherapeutic strategies including vaccines and checkpoint inhibitors have been studied to improve the effectiveness of the immune system in destroying cancer cells. Recent studies have shown that kinase inhibitors, capable of inhibiting signal transduction cascades that affect cell proliferation, migration, and angiogenesis, have additional immunological effects. In this review, we explain the beneficial therapeutic effects of novel small-molecule kinase inhibitors and explore how, through different mechanisms, they increase the protective antitumor immune response in high-grade brain tumors.

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“…Entrectinib, [16] an inhibitor targeting tropomyosin receptor kinases (Trk), protooncogene tyrosine-protein kinase ROS1, and anaplastic lymphoma kinase (ALK), is indicated for metastatic non-small cell lung cancer (NSCLC) with ROS1 or NTRK gene fusions. Axitinib, [17][18] a vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor, finds its application in advanced renal cell carcinoma (kidney cancer) after prior systemic therapy. Lonidamine [19] possesses antineoplastic properties and has been explored for its potential in cancer treatment by disrupting cancer cell energy metabolism, although its adoption as a standard cancer treatment remains limited.…”

Section: Introductionmentioning

confidence: 99%

2‐(1‐Methyl‐1H‐indazol‐5‐yl)‐N‐arylisonicotinamide Analogs: Synthesis, Anticancer Screening, SAR and ADMET Studies

Patel,

Unjiya,

Dabhi

et al. 2024

ChemistrySelect

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In this current research framework, we detailed the synthesis of ten novel 2‐(1‐methyl‐1H‐indazol‐5‐yl)‐N‐arylisonicotinamide analogs (3a–j). The synthesis of these compounds (3a–j) involved a three‐step process, employing the Suzuki‐Miyaura coupling reaction, which successfully linked 1‐methyl‐1H‐indazole with isonicotinamide to satisfactory yields. The synthesized compounds were characterized using various spectroscopic techniques. To assess their potential, the anticancer activity of compounds (3a–j) was evaluated following the National Cancer Institute (NCI US) protocol against nine panels comprising different cancer cell lines, at a concentration of 10−5 M. Growth percentage (GP) and percentage growth inhibition (PGI) were calculated for each compound. Notably, the CNS cancer cell line SNB‐75 exhibited a remarkable PGI of 99.16 percent, indicating high sensitivity to the tested compound 3e. Additionally, ADMET prediction suggested that most of the synthesized compounds possess drug‐like properties, with low adverse effects and toxicity. These findings represent a significant advancement, offering potential avenues for further developments in the field of cancer research.

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Losartan Alleviates the Side Effects and Maintains the Anticancer Activity of Axitinib

Cited by 8 publications

References 24 publications

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management

2‐(1‐Methyl‐1H‐indazol‐5‐yl)‐N‐arylisonicotinamide Analogs: Synthesis, Anticancer Screening, SAR and ADMET Studies

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