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Pazopanib in advanced soft tissue sarcomas.

Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma (STS). Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors, preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling pathways. Following the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma, pazopanib was investigated in STS. A landm

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… Phase 1 study of pazopanib alone or combined with lapatinib in Japanese patients with solid tumors. Cancer Chemother. Pharmacol. 2014;73:673–683. doi: 10.1007/s00280-014-2374-3. 24. Kalow W. Interethnic variation of drug metabolism. Trends Pharmacol. …

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

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… Augmentation of HER2 occurs in 20–25 % of breast cancer types, and HER2-targeted therapy (trastuzumab and lapatinib) has been reported to increase life expectancy by 50 %. …

Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing.

Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence of drug resistance further complicates therapeutic efficacy, underscoring the urgent need for alternative approaches. Drug repurposing, characterized by the utilization of existing drugs for novel clinical applications, emerges as a promising avenue for addressing these challenges. Repurposed d

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… Jubie et al. reported that analogs of ABZ and MBZ exhibited potent cytotoxicity comparable to Lapatinib in BC cells overexpressing HER2 [ 55 ]. …

Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.

Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interaction

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… TdP (n=245) | Capecitabine (L01BC06) | 91 (6.8) Imatinib (L01XX28) | 61 (4.6) Bortezomib (L01XX32) | 22 (1.6) Bendamustine (L01AA09) | 21 (1.5) 5-Fluorouracil (L01BC02) | 21 (1.5) Nilotinib (L01XE08) | 10 (0.7) Dasatinib (L01XE06) | 7 (0.5) Tamoxifen (L02BA01) | 6 (0.4) Epirubicin (L01DB03) | 2 (0.1) Lapatinib …

Dermatologic conditions in women receiving systemic cancer therapy.

As advances in cancer therapies have improved cancer-related survival, novel therapeutics have also introduced a variety of dermatologic toxicities, and an increased number of patients are living with these sequalae. Women with cancer in particular experience a spectrum of dermatologic conditions that affect their skin, hair, nail, and mucosal surfaces. Studies have shown that these toxic effects can significantly affect quality of life and alter a woman's self-image, cultural identity, femininity, sexuality, and mental health. In severe instances, dermatologic toxicities may even disrupt canc

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… , gastric, lung, lymphomas Targeted therapy EGFR inhibitors/HER1 inhibitors | Cetuximab | Head and neck, colorectal | Panitumumab | Colorectal | Erlotinib | Lung, pancreatic | Gefitinib | Non-small cell lung HER2 inhibitors | Trastuzumab | Breast | Pertuzumab | Breast EGFR/HER2 inhibitors | Lapatinib … EGFR inhibitors are correlated with a higher frequency and severity of the papulopustular eruption, with rates as high as 85%, particularly among patients treated with monoclonal antibodies (cetuximab, panitumumab) compared with those treated with tyrosine kinase inhibitors (erlotinib, gefitinib, lapatinib …

Mitophagy related gene signature for prognosis and therapeutic evaluation in KIRC.

This study conducted a comprehensive investigation of the prognostic significance and immunological features associated with mitophagy-related gene signatures in clear cell renal cell carcinoma (KIRC). Our primary aim was to establish an optimized predictive model for precise prognosis stratification and treatment response prediction in KIRC patients. Through LASSO Cox regression analysis, we systematically identified mitophagy-related genes (MRGs) and implemented them to develop a prognostic risk stratification model. The model's reliability was rigorously validated using both internal cohort

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… The results indicated that Bortezomib exhibited a lower IC50 value in the high-risk group, suggesting its potential for these patients’ treatment, whereas the low-risk group might benefit from treatments with Bryostatin, Genentech Cpd 10, Lapatinib, Imatinib, IPA-3, Midostaurin, Obatoclax Mesylate, and …

Targeted synthesis of a trimethoxyphenyltetrahydropyrimidine analogue designed as a DNA intercalator: in silico, multi-spectroscopic, thermodynamic, and in vitro approaches.

Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T1-35). The designed analogues (T1-35) were investigated for their inhibitory potential towards the hybrid DNA and Topo-II target receptor using molecular docking. Interestingly, the theoretically designed analogue T30 with a 3,4,5-trimethoxy phenyl side chain was found to be the superior candidate, achieving a binding score of -7.06 kcal m

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… -Y. et al. , Exploring the binding interaction of calf thymus DNA with lapatinib, a tyrosine kinase inhibitor: multi-spectroscopic techniques combined with molecular docking J. Biomol. Struct. Dyn. 2019 37 3 576 583 29375016 10.1080/07391102.2018.1433067 Sirajuddin M. Ali S. Badshah A. …

Frequently asked questions on surrogate endpoints in oncology-opportunities, pitfalls, and the way forward.

Patients with cancer expect prolonged life (overall survival, OS) or better life (quality of life, QOL) from cancer treatments. However, majority of new cancer drugs are now being approved not based on improved OS or QOL, but based on surrogate endpoints such as tumor shrinkage or delayed tumor progression. These surrogate endpoints, including their validity as a proxy for overall survival, differ based on disease settings and lines of treatment but in general, most surrogate measures have weak correlation with outcomes that matter to patients. Nevertheless, they are being increasingly used as

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… Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol. 2020;38(27):3138–3149. doi: 10.1200/JCO.20.00147. 102. …

Side Effects of Novel Anticancer Drugs on the Posterior Segment of the Eye: A Review of the Literature.

Currently, common treatment approaches for neoplastic diseases include surgery, radiation, and/or anticancer drugs (chemotherapy, hormone medications, and targeted therapies). In particular, anticancer medicines destroy cancerous cells by blocking certain pathways that aid in the disease's initiation and progression. These pharmaceutical drugs' capacity to inhibit malignant cells has made them indispensable in the treatment of neoplastic disorders. Nonetheless, considering their cyto- and neurotoxicity, as well as their inflammatory responses, these medications may also have unfavorable system

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… According to the Food and Drug Administration (FDA) and the published scientific literature, only trastuzumab has been linked to retinal side effects, whereas pertuzumab, lapatinib, neratinib, and tucatinib have not been linked to any ocular side effects. …

Ocular Surface Side Effects of Novel Anticancer Drugs.

Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and/or radiation are common treatment strategies for neoplastic diseases. Anticancer drugs eliminate malignant cells through the inhibition of specific pathways that contribute to the formation and development of cancer. Given the ability of such pharmacological medications to combat cancerous cells, their role in the management of neoplastic diseases has become essential. However, these drugs may also lead to undesirable systemic and ocular adverse effects due to cyto/neuro-toxicity and inflammatory reactio

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… Regarding ocular surface adverse effects, the FDA and literature have not reported any ocular side effects for lapatinib, neratinib, or tucatinib, while there have been recorded ophthalmic side effects for trastuzumab and pertuzumab. …

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential t

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… | Chronic myeloid leukemia (CML) Receptor tyrosine kinase inhibitors | | Afatinib | 5 EGFR | Non-small cell lung cancer (NSCLC) Erlotinib | EGFR | Non-small cell lung cancer (NSCLC) Gefitinib | EGFR | Non-small cell lung cancer (NSCLC) Gilteritinib | ALK kinase, AXL | Acute myeloid leukemia (AML) Lapatinib …

Methodology and results of real-world cost-effectiveness of carfilzomib in combination with lenalidomide and dexamethasone in relapsed multiple myeloma using registry data.

OBJECTIVE: To predict the real-world (RW) cost-effectiveness of carfilzomib in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in relapsed multiple myeloma (MM) patients after one to three prior therapies. METHODS: A partitioned survival model that included three health states (progression-free, progressed disease and death) was built. Progression-free survival (PFS), overall survival (OS) and time to discontinuation (TTD) data for the Rd arm were derived using the Registry of Monoclonal Gammopathies in the Czech Republic; the relative treatmen

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… Delea TE Amdahl J Chit A Amonkar MM Cost-effectiveness of lapatinib plus letrozole in her2-positive, hormone receptor-positive metastatic breast cancer in Canada Curr. Oncol. (Toronto Ont.) 2013 20 5 e371 e387 10.3747/co.20.1394 PMC3805407 24155635 45. …

Translational nanoparticle engineering for cancer vaccines.

Conventional cancer treatments remain insufficient to treat many therapy-resistant tumors.1 Cancer vaccines attempt to overcome this resistance by activating the patient's immune system to eliminate tumor cells without the toxicity of systemic chemotherapy and radiation. Nanoparticles (NPs) are promising as customizable, immunostimulatory carriers to protect and deliver antigen. Although many NP vaccines have been investigated in preclinical settings, a few have advanced into clinical application, and still fewer have demonstrated clinical benefit. This review incorporates observations from NP

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… | Concurrent with, after, or without cisplatin and vinorelbine | 28 | Phase I | 4 arms, NR, DE | 61 | NUC | Safety/Humoral response | pos/pos | NR//pos | Stage II–III HER2-+ breast cancer | | 20 | Phase I | NR, NB | 12 | NUC | Safety/Humoral immunity | pos/pos | neg//pos | HER2+ breast cancer | Lapatinib …

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.

Antibody-drug conjugates (ADCs) represent a transformative class of targeted therapies designed to deliver potent cytotoxic agents specifically to tumor cells, minimizing systemic toxicity. This review provides a comprehensive overview of ADCs, detailing their mechanisms of action, design strategies, and clinical advancements. ADCs utilize monoclonal antibodies to selectively bind tumor-associated antigens, enabling the precise delivery of toxic payloads to cancer cells. The review explores the critical components of ADCs, including the antibody, linker, and payload, and highlights how these e

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… In the phase 3 EMILIA trial of 991 patients with previously treated HER2-positive advanced breast cancer, T-DM1 significantly improved progression-free survival (9.6 vs. 6.4 months; HR 0.65; p < 0.001) and overall survival (30.9 vs. 25.1 months; HR 0.68; p < 0.001) compared with lapatinib plus capecitabine … Compared to lapatinib plus capecitabine, T-DM1 significantly improved PFS (9.6 months vs. 6.4 months) and OS (30.9 months vs. 25.1 months), with a better safety profile [ 17 ]. …

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, s

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… ERBB3, in particular, has been linked to lapatinib sensitivity induced by the HBV-X protein [ 94 ]. The ERBB family members (ERBB2, ERBB3, and ERBB4) are also the dominant receptors for neuregulin 1 (NRG1), which has been identified as a positive regulator of the HCC EMT and metastasis [ 95 ]. …

Cardiac Interventions in Patients With Active, Advanced Solid and Hematologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit con

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… Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial Lancet Oncol 18 6 2017 732 742 10.1016/S1470-2045(17)30312- …

Expert consensus on the clinical application of antibody-drug conjugates in the treatment of malignant tumors (2021 edition).

Antibody-drug conjugates (ADCs) are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. It is necessary for clinicians to understand the molecular characteristics and mechanisms of ADCs. Patients' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. This consensus provides a systematic review of commercially available ADCs a

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… The results of the EMILIA study ( n = 991) showed that T‐DM1 significantly prolonged median PFS (9.6 and 6.4 months; HR = 0.65, p < 0.001) and median OS (30.9 and 25.1 months; HR = 0.68; p < 0.001) compared with lapatinib + capecitabine patients with HER2‐positive advanced breast cancer pretreated by …

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer.

Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic br

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… Interleukin-6 expression contributes to lapatinib resistance through maintenance of stemness property in HER2-positive breast cancer cells . Oncotarget . ( 2016 ) 7 : 62352 – 63 . 10.18632/oncotarget.11471 27694691 PMC5308732 85. Liu C Dong L Sun Z Wang L Wang Q Li H . …

An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of