Ponatinib: An update on its drug targets, therapeutic potential and safety

Gao, Yue; Ding, Yongsheng; Tai, Xuguang; Zhang, Chen; Wang, Dong

doi:10.1016/j.bbcan.2023.188949

Cited by 7 publications

(3 citation statements)

References 114 publications

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“…Significant cardiovascular toxicity is a challenge for the clinical use of the 3rdG TKI ponatinib. Thus, developing strategies to minimize its toxicity and side effects is necessary [ 24 ]. The PACE trial reported a cumulative 5-year incidence rate of AOEs of 31% (serious AOEs, 26%) in the chronic-phase CML population; there was a correlation between a longer duration of treatment with ponatinib and a higher cumulative incidence rate.…”

Section: Discussionmentioning

confidence: 99%

The new Systematic Coronary Risk Evaluation (SCORE2 and SCORE2-OP) estimates the risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib or ponatinib

Mulas,

Abruzzese,

Luciano

et al. 2023

Ann Hematol

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Patients with chronic myeloid leukemia (CML) treated with nilotinib or ponatinib may experience arterial occlusive events (AOEs). It is currently recommended to thoroughly assess cardiovascular risk factors before treating CML. We identified 455 consecutive CML adult patients, 335 treated with nilotinib and 120 with ponatinib; 380 patients without previous cardiovascular diseases or diabetes were stratified according to the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Older Persons (SCORE2-OP). This updated algorithm from the European Society of Cardiology (ESC) estimates a 10-year risk of fatal and non-fatal cardiovascular diseases. It is based on sex, age, smoking habits, systolic blood pressure, non-high-density lipoprotein cholesterol, and European geographical region of cardiovascular risk. The SCORE2/SCORE2-OP algorithm translated more patients (50.2%) to the high–very high cardiovascular risk category than the previous SCORE (25.3%). Patients with a high to very high SCORE2/SCORE2-OP risk showed a significantly higher incidence rate of AOEs (69.2% vs. 46.5%, p < 0.001). The older SCORE was less specific in estimating AOEs in patients classified as low-intermediate risk (69.8 vs. 54.2%). In multivariate analysis, no associations were found between AOEs and gender, age, and type or dose of tyrosine kinase inhibitor. Only the SCORE2/SCORE2-OP risk was confirmed as a significant predictive factor (p = 0.028; hazard ratio = 2.2; 95% confidence interval = 1.1–4.5). Patients with AOEs required, in most cases, imaging diagnostic tests, additional drugs, and sometimes invasive procedures, increasing access to visits and hospital management. This real-life study suggested that the SCORE2 and SCORE2-OP charts could help identify cardiovascular fragility in CML patients providing them with more attention and a proper TKI selection.

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Section: Discussionmentioning

confidence: 99%

The new Systematic Coronary Risk Evaluation (SCORE2 and SCORE2-OP) estimates the risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib or ponatinib

Mulas,

Abruzzese,

Luciano

et al. 2023

Ann Hematol

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“…Ponatinib, with a MW of approximately 569 Da, is primarily used for the treatment of chronic myeloid leukemia (CML). It is a potent tyrosine kinase inhibitor that targets a range of kinases, including BCR-ABL, which is associated with CML, as well as kinases such as VEGFR-2, SRC, KIT, and PDGFR [50]. Lenvatinib, characterized by an MW of approximately 426.88 Da, is a tyrosine kinase inhibitor applied in the treatment of differentiated thyroid cancer and hepatocellular carcinoma, with FDA approval for these specific oncological indications.…”

Section: Vegfi Belonging To the Small Molecules Categorymentioning

confidence: 99%

Exploring the Spectrum of VEGF Inhibitors’ Toxicities from Systemic to Intra-Vitreal Usage in Medical Practice

Santorsola,

Capuozzo,

Nasti

et al. 2024

Cancers

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The use of Vascular Endothelial Growth Factor inhibitors (VEGFi) has become prevalent in the field of medicine, given the high incidence of various pathological conditions necessitating VEGF inhibition within the general population. These conditions encompass a range of advanced neoplasms, such as colorectal cancer, non-small cell lung cancer, renal cancer, ovarian cancer, and others, along with ocular diseases. The utilization of VEGFi is not without potential risks and adverse effects, requiring healthcare providers to be well-prepared for identification and management. VEGFi can be broadly categorized into two groups: antibodies or chimeric proteins that specifically target VEGF (bevacizumab, ramucirumab, aflibercept, ranibizumab, and brolucizumab) and non-selective and selective small molecules (sunitinib, sorafenib, cabozantinib, lenvatinib, regorafenib, etc.) designed to impede intracellular signaling of the VEGF receptor (RTKi, receptor tyrosine kinase inhibitors). The presentation and mechanisms of adverse effects resulting from VEGFi depend primarily on this distinction and the route of drug administration (systemic or intra-vitreal). This review provides a thorough examination of the causes, recognition, management, and preventive strategies for VEGFi toxicities with the goal of offering support to oncologists in both clinical practice and the design of clinical trials.

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“…Bosutinib is a multikinase inhibitor with activity against ABL, SRC, TEC and STE family of kinases, CAMK2G, and ErbB3; however, it does not inhibit KIT and PDGFR [ 14 , 15 ]. Ponatinib is known to target not only BCR-ABL but also RET, FLT3, BRAF, MEKK2, KIT, SRC, DDR1, Tie2, PDGFR, fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor receptor (VEGFR) family members [ 16 , 17 ]. The differential target spectra of TKIs can explain differences in their off-target effects and toxicities via the non-selective inhibition of other targets [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Keratosis Pilaris-like Eruption during Treatment of Chronic Myeloid Leukemia with Tyrosine Kinase Inhibitors: Literature Review and Report of a Case Related to Imatinib

Ambrogio,

Poli,

Lospalluti

et al. 2023

JCM

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The advent of tyrosine kinase inhibitors (TKIs) blocking BCR-ABL activity has revolutionized the therapeutic management of patients with chronic myeloid leukemia (CML). Adverse cutaneous reactions (ACRs) are common nonhematologic adverse events associated with the use of BCR-ABL TKIs. A characteristic pattern of eruption resembling keratosis pilaris (KP) has been described in patients treated with these drugs, especially nilotinib and dasatinib. The pathogenesis of this ACR is still unknown. This type of reaction appears to be uncommon with imatinib. Here, we report the case of an elderly patient with an asymptomatic KP-like eruption, which appeared one month after starting treatment with imatinib for CML. The case presentation is accompanied by a review of similar reactions in patients with CML treated with BCR-ABL inhibitors, attempting to make an excursus on the molecular targets of such drugs and possible mechanisms underlying this ACR.

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Ponatinib: An update on its drug targets, therapeutic potential and safety

Cited by 7 publications

References 114 publications

The new Systematic Coronary Risk Evaluation (SCORE2 and SCORE2-OP) estimates the risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib or ponatinib

The new Systematic Coronary Risk Evaluation (SCORE2 and SCORE2-OP) estimates the risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib or ponatinib

Exploring the Spectrum of VEGF Inhibitors’ Toxicities from Systemic to Intra-Vitreal Usage in Medical Practice

Keratosis Pilaris-like Eruption during Treatment of Chronic Myeloid Leukemia with Tyrosine Kinase Inhibitors: Literature Review and Report of a Case Related to Imatinib

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