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Current and Emerging Therapy for Malignant Pleural Mesothelioma: Focus on CD26/Dipeptidyl Peptidase IV as a Therapeutic Target

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… Unfortunately, phase I and phase II clinical trials involving the mTKIs sorafenib, sunitinib, pazopanib, and desatinib showed either limited anti-mesothelioma activity, the inability to induce remission, and/or unacceptable toxicity [ 48 - 52 ]. … Brief report: A phase II study of sunitinib in malignant pleural mesothelioma. The NCIC Clinical Trials Group. J. Thorac. Oncol. 2011;6(11):1950–1954. doi: 10.1097/JTO.0b013e3182333df5. 51. Dudek A.Z., Pang H., Kratzke R.A., et al. …

Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines.

Fibroblast growth factor receptor (FGFR) tyrosine kinases, which are expressed on the cell membrane, are involved in a wide range of biological functions such as cell proliferation, survival, migration, and differentiation. The identification of FGFR fusions and other alterations in a wide range of solid tumors, including cholangiocarcinoma and bladder cancer, has resulted in the development of several selective FGFR inhibitors for use in these indications, for example, infigratinib, erdafitinib, derazantinib, pemigatinib, and futibatinib. In addition to the typical adverse events associated w

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… The effect of hand‐foot skin reaction associated with the multikinase inhibitors sorafenib and sunitinib on health‐related quality of life . J Drugs Dermatol 2012 ; 11 : e61 – e65 . 23135095 47 Huggins RH , Kuzel TM , Anderson RT et al. … Hand foot skin reaction (HFSR) by the multikinase inhibitors (MKIs) sorafenib and sunitinib: Impact on quality of life (QoL) . J Clin Oncol 2008 ; 26 ( suppl 15 ): 16122a . 48 Anderson R , Jatoi A , Robert C et al. …

Autophagy in tumor immune escape and immunotherapy.

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of immune resistance remains significant. Autophagy, a cellular response to various stressors, involves the degradation of damaged proteins and organelles via lysosomal pathways, maintaining cellular homeostasis. This process not only supports tumor cell survival but also profoundly impacts the efficacy of cancer immunotherapies. The modulation of autophagy in tumor cells or immune cells exerts dual effects on tumor immune escape and immunotherapy. However,

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… For example, Sunitinib, Andrographolide, and zosuquidar enhance p62-dependent selective autophagic degradation of PD-L1, thereby boosting anti-tumor immunity [ 55 – 57 ]. … The Beneficial Role of Sunitinib in Tumor Immune Surveillance by Regulating Tumor PD-L1. Adv Sci (Weinh). 2021;8:2001596. 33510997 10.1002/advs.202001596 PMC7816704 56. …

Knowledge, Attitude, and Management of General Dentist toward Medication-related Osteonecrosis of the Jaws.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is an intense negative drug response causing increasing bone destruction in the maxillofacial area of patients. AIMS AND OBJECTIVES: To evaluate the knowledge and attitude of dental practitioner regarding risk factors of MRONJ in Saudi Arabia. MATERIALS AND METHODS: A cross-sectional, questionnaire survey was carried out in King Khalid Hospital, Al-Kharj among dental practioners. RESULTS: Approximately 60% of the practioners had a poor knowledge and there was a weak positive correlation with work experience. CONCLUSION: Poor k

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… The second is tyrosine kinase inhibitor (e.g., sunitinib), which inhibits the tyrosine kinase receptor; both medication is antiangiogenic that has been believed to facilitate the antineoplastic agents delivery. …

Mitochondrial Determinants of Anti-Cancer Drug-Induced Cardiotoxicity.

Mitochondria are key organelles for the maintenance of myocardial tissue homeostasis, playing a pivotal role in adenosine triphosphate (ATP) production, calcium signaling, redox homeostasis, and thermogenesis, as well as in the regulation of crucial pathways involved in cell survival. On this basis, it is not surprising that structural and functional impairments of mitochondria can lead to contractile dysfunction, and have been widely implicated in the onset of diverse cardiovascular diseases, including ischemic cardiomyopathy, heart failure, and stroke. Several studies support mitochondrial t

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… Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib Lancet 2007 370 2011 2019 10.1016/S0140-6736(07)61865-0 18083403 PMC2643085 158. Wang Z. ErbB Receptors and Cancer Methods Mol. Biol. 2017 1652 3 35 28791631 10.1007/978-1-4939-7219-7_1 159. Kenigsberg B. Jain V. Barac A. … Sunitinib-induced cardiotoxicity is mediated by off-target inhibition of AMP-activated protein kinase Clin. Transl. Sci. 2009 2 15 25 10.1111/j.1752-8062.2008.00090.x 20376335 PMC2849142 164. Will Y. Dykens J.A. Nadanaciva S. Hirakawa B. Jamieson J. Marroquin L.D. Hynes J. Patyna S. Jessen B.A. …

The concept of exceptionality: a legal farce?

How do we decide which treatments should be offered by the National Health Service (NHS) when we cannot afford to fund them all? In the absence of a positive appraisal by the National Institute for Health and Clinical Excellence (NICE), which mandates the provision of a treatment by the NHS, Primary Care Trusts (PCTs) are free to decide whether to provide a particular drug to some, or all, of their population. However, as public bodies, it is a well-established principle of Administrative Law that PCTs are not at liberty to fetter the exercise of their own discretion. They must recognise the p

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… Jean Murphy initially received two months funding for sunitinib from a private benefactor. She then reapplied to Salford PCT for funding, on the basis that she had responded unusually well to the drug. On this occasion, her IFR was approved. … For sunitinib alone, a drug used to treat kidney cancer, it is alleged the NHS has failed to reclaim nearly £4 million. For more detail see S Williamson and T Thomson, ‘A Report Into the Uptake of Patient Access Schemes in the NHS’ (2010) 2 Clinical Pharmacist 268–70. …

Medication-Related Osteonecrosis of the Jaw: A Systematic Review of Case Reports and Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare condition, typically seen in patients receiving antiresorptive or antiangiogenic drugs. This study aims to synthesize reports and case series of MRONJ regarding sociodemographic and clinical characteristics and to evaluate the effectiveness of the treatments applied. Following PRISMA guidelines, a search for case reports and case series was carried out in the PubMed-Medline database until March 2024. A total of 88 articles were included in this review, in a total of 151 cases. The key findings reveal that females were the most affec

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… When it comes to recognized risk factors of MRONJ, antiresorptive medications such as bisphosphonates or denosumab and antiangiogenic medications such as aflibercept and sunitinib are associated with an increased risk of developing MRONJ [ 11 ]. … The 10 most frequently associated drugs were, in descending order, zoledronic acid, alendronic acid, denosumab, pamidronic acid, ibandronic acid, lenalidomide, risedronic acid, sunitinib, bevacizumab, and prednisolone. …

Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications.

Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several m

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… Thalidomide, sorafenib and sunitinib are in various phases of clinical investigation [ 18 , 19 , 20 ] and a replicative competent adenovirus that targets the VEGF promoter is being tested preclinically [ 21 ]. … Phase II study of sunitinib as second-line therapy in malignant pleural mesothelioma (MPM) J. Clin. Oncol. 2008 doi: 10.1200/jco.2008.26.15_suppl.8063. 21. Harada A., Unchino J., Harada T., Nakagaki N., Hisasue J., Fujita M., Takayama K. …

Clinical impact of checkpoint inhibitors as novel cancer therapies.

Immune responses are tightly regulated via signaling through numerous co-stimulatory and co-inhibitory molecules. Exploitation of these immune checkpoint pathways is one of the mechanisms by which tumors evade and/or escape the immune system. A growing understanding of the biology of immune checkpoints and tumor immunology has led to the development of monoclonal antibodies designed to target co-stimulatory and co-inhibitory molecules in order to re-engage the immune system and restore antitumor immune responses. Anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies were among t

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… Initial reports from phase I trials combining nivolumab with vascular endothelial growth factor (VEGF)-targeted therapies (sunitinib or pazopanib) are currently under study to determine the best dose and schedule [ 67 , 68 ]. … Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014;32(8):760–767. doi: 10.1200/JCO.2013.50.3961. 33. Motzer R, Rini B, McDermott D, et al. …

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug-drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncol

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… inhibitor 70.2% Gastric S-1 (Tegafur, gimeracil, oteracil) No No No 52% (Tegafur) Skin Sonidegib Substrate No Inhibitor >97% GIST, Kidney, Liver, Melanoma,Thyroid Sorafenib Inhibitor and substrate Inhibitor and substrate No 99% NETs Streptozocin N/A N/A N/A N/A GIST, Kidney, NETs, Thymoma, Thyroid Sunitinib … For example, the area under the curve of sunitinib and nilotinib was increased by 11% and 29%, respectively, because of grapefruit, a well-known CYP3A4 inhibitor [ 31 ] (Tables 3 and 4 ). Some many other foods or herbs may potentially influence the pharmacokinetic parameters of oral anticoagulants. …

Acute interstitial nephritis - a reappraisal and update.

Acute interstitial nephritis (AIN) is an under recognized and under diagnosed cause of acute kidney injury (AKI). It is estimated to account for 15 - 20% of cases of AKI; it is the reported diagnosis in 2.8% of all kidney biopsies, and 13.5% of biopsies done specifically for acute renal failure. Considerable evidence implicates antigen initiated cell-mediated injury in the pathogenesis of AIN. Drugs account for 70% of all cases, with over 150 different agents incriminated. The remaining cases are due to infections, autoimmune diseases, and rarely idiopathic. The central component of renal inju

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… > esmoprazole > rabeprazole; H2 Antagonists: cimetidine, famotidine, ranitidine Drug-induced: anti-neoplastic agents Incidence >20 cases reported Ifosfamide Other agents: adriamycin, BCG, bevacizumab, carboplatin, cediranib, gemcitabine, ipilimumab, interferon, lenolidomide, pemetrexed, sorafenib, sunitinib … Semin Nephrol . 2003 ; 23 : 500 – 508 . 13680539 10.1016/s0270-9295(03)00094-9 72 Winn SK Ellis S Savage P Sampson S Marsh JE Biopsy-proven acute interstitial nephritis associated with the tyrosine kinase inhibitor sunitinib: a class effect? …

Cardio-Oncology and Multi-Imaging Modalities.

Early detection and the rise of targeted cancer treatment have led to increased overall survival and decreased mortality among cancer patients. As the cancer survivor population ages, there is an increased risk for cardiovascular disease due to pre-existing comorbidities, deconditioning during therapy, or the natural progression of aging. Furthermore, with emerging oncologic therapies, there is an increased recognition of their potential cardiovascular toxicities. Indeed, heart disease is the leading cause of death in cancer survivors, which may reflect upon both the success of novel oncologic

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… Select VEGF Inhibitors Certain VEGF inhibitors (i.e., pazopanib and sunitinib) are associated with heart failure, atherosclerotic heart disease, or the development of hypertension [ 42 , 45 ]. … Cardiotoxicity Associated with Tyrosine Kinase Inhibitor Sunitinib Lancet 2007 370 2011 2019 10.1016/S0140-6736(07)61865-0 18083403 PMC2643085 46. Santoni M. Guerra F. Conti A. Lucarelli A. Rinaldi S. Belvederesi L. Capucci A. Berardi R. …

Clinical evaluation and outcome in heart failure patients receiving chemotherapy with different anti-cancer agents.

BACKGROUND: The optimal strategy for modern chemotherapy should be based on a comprehensive approach for cancer patients with cardiovascular diseases. Therefore, cardio-oncology has received increasing attention owing to the cardiotoxic effects of anti-cancer therapies. OBJECTIVES: We aimed to evaluate the clinical characteristics and outcomes of patients with heart failure (HF) who received chemotherapy compared with those of a matched cohort with HF who did not receive chemotherapy, using real-world HF data. METHODS: This study was based on the Diagnosis Procedure Combination (DPC) databas

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… : afatinib for the treatment of non‐small cell lung cancer, lapatinib for the treatment of breast cancer and vandetanib for the treatment of other types of cancer, such as thyroid cancer. 24 , 25 The risk of HF is highest in the initial stages of therapy, with 33.8% of patients receiving sorafenib, sunitinib … Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma . J Clin Oncol 2008 ; 26 : 5204 ‐ 5212 . doi: 10.1200/JCO.2007.15.6331 18838713 27 Totzeck M , Mincu RI , Mrotzek S , Schadendorf D , Rassaf T . …

Acute Kidney Injury Associated with Anticancer Therapies: Small Molecules and Targeted Therapies.

Molecular targeted therapy has revolutionized cancer treatment by significantly improving patient survival compared with standard conventional chemotherapies. The use of these drugs targets specific molecules or targets, which block growth and spread of cancer cells. Many of these therapies have been approved for use with remarkable success in breast, blood, colorectal, lung, and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drugs effectively with high specificity while being less toxic. Although known as "targeted," many of these agents lack specifici

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… tumor growth and metastasis. 5 Several strategies are available for inhibiting VEGF/VEGFR signaling. mAbs, such as bevacizumab, or fusion proteins, such as aflibercept, can inhibit VEGF, while fully humanized Abs, such as ramucirumab, target VEGFR, and multi-tyrosine kinase inhibitors (mTKIs), such as sunitinib … h/approximately 100%/25 L/h | AKI Proteinuria | Monitor kidney functions | Delay new cycle if CTCAE grade 3 AKI | 27 CD30-directed antibody | Brentuximab | 4–6 d/unk/unk | Worsens already present kidney impairment | Stop drug and go for HSCT if CR | Avoid if CrCl <30 ml/min | 28 ALK/cMET | Imatinib Sunitinib …

Oncolytic virotherapy as emerging immunotherapeutic modality: potential of parvovirus h-1.

Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evide

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… Combination of the oncolytic virus with cytostatic (cisplatin, vincristine) or targeted (sunitinib) drugs resulted in a further increase in melanoma cell apoptosis but failed to strengthen maturation of DCs. … Interestingly, the interleukin profile of DCs was altered upon exposure to H-1PV plus sunitinib-cotreated TCLs. …

Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison.

Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor ac

A Systematic Review of Laser Photobiomodulation Dosimetry and Treatment Protocols in the Management of Medications-Related Osteonecrosis of the Jaws: A Rationalised Consensus for Future Randomised Controlled Clinical Trials.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or comb

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… Antiangiogenic Drugs These medications are tyrosine-kinase inhibitors: sunitinib/sorafenib, monoclonal antibodies targeting VEGF, preventing the formation of new blood vessels binding to various signalling molecules and inhibiting angiogenesis. … It is utilised in the treatment of malignant diseases of the kidneys, gastrointestinal tract and lungs, as well as glioblastoma [ 35 , 36 ], whereas Sunitinib is used in the treatment of metastatic renal carcinoma and neuroendocrine tumours of the pancreas. …

Drug Repurposing of New Treatments for Neuroendocrine Tumors.

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metas

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… For localized disease, curative radical surgery represents the standard of care, while for locally advanced unresectable or metastatic NETs, many systemic options are approved and available, including somatostatin analogues (SSAs), targeted therapies such as everolimus or sunitinib, peptide receptor … Randomized phase III studies assessing SSAs, targeted therapies such as everolimus and sunitinib, and PRRT have shaped the present treatment guidelines. Unfortunately, the reduced number of head-to-head studies has hindered the establishment of the best treatment sequence. …

Dethroning of Neuroendocrine Tumor as an Orphan Disease: US Incidence, Prevalence, and Survival in the 21st Century.

Importance: Neuroendocrine tumors (NETs) have traditionally been considered rare (orphan) diseases; however, improvements in diagnostic methods and heightened awareness about NETs may have altered their epidemiologic profile in the U.S. Objective: To evaluate trends in incidence, prevalence, and survival of NETs in the United States from 2000 to 2021 using updated data from the SEER-22 registry. Method: This population-based, retrospective cohort study used the SEER-22 database for incidence, prevalence, and survival analyses. Data included 231,659 patients diagnosed with NETs between 2000 and

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… In 2011, the RADIANT-3 trial showed that everolimus improved progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors compared to placebo (median: 11 versus 4.6 months), while the SUN1111 trial found that sunitinib enhanced both PFS (median: 11.4 versus 5.5 months) and … Sunitinib in pancreatic neuroendocrine tumors: Updated progression-free survival and final overall survival from a phase III randomized study. Ann. Oncol. 2017;28:339–343. doi: 10.1093/annonc/mdw561. 11. …

Atrial Cardiomyopathy and Atrial Fibrillation in Cancer.

The number of patients with oncologic and cardiologic comorbidities is increasing. A growing number of evidence shows an inextricable link between cancer, atrial fibrillation, and atrial cardiomyopathy. Cancer itself and resultant inflammation, anticancer treatment, and other comorbidities lead to atrial remodeling and fibrosis, which increases the tendency to develop atrial cardiomyopathy and atrial fibrillation. The scarcity of current literature and ambiguous results make its relationship difficult to fully understand. In this review, we will summarize existing evidence of the relationships

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… AF could also occur in patients treated with other anticancer drugs such as fluorouracil, methotrexate, alkylating agents, antimicrotubule agents (docetaxel, paclitaxel), tyrosine kinase inhibitors (imatinib, lapatinib, sunitinib), proteasoma inhibitor (bortezomib), bevacizumab (blocker of the vascular … Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma BMC Cancer 2010 10 p. 489 10.1186/1471-2407-10-489 20840755 PMC2946311 50 Wollersheim B. M. Boekhout A. H. van der Poel H. …