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Cardiac Cachexia: Unaddressed Aspect in Cancer Patients.

Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are au

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… for 11 days and sacrificed on 12 th day | Doxo: a 20% decrease in [LV(dP/dt) max] and a 33% decrease in [LV(dP/dt) min] ; paclitaxel: No significant changes; doxo + paclitaxel: a 39% decrease in [LV(dP/dt) max] and a 46% decrease [LV(dP/dt) min ] | [ 87 ] 3 | Tyrosine kinase inhibitors: gefitinib, lapatinib … On the 5th day, cells were treated with drugs, and after 3 days, cells were lysed to measure LDH activity | Lapatinib, erlotinib, gefitinib: no cardiotoxicity; imatinib, sorafenib: mild; sunitinib, dasatinib: moderate toxicity. …

The updated landscape of tumor microenvironment and drug repurposing.

Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly b

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… intervention Cervical cancer NCT01902966 Active, not recruiting Metformin Immunotherapy (nivolumab, pembrolizumab, sintilimab) NSCLC, SCLC, melanoma, solid tumors NCT03048500 ; NCT03311308 ; NCT03874000 ; NCT03874000 Recruiting NCT02145559 Completed Targeted therapy (temsirolimus, vandetanib, sirolimus, lapatinib … Cervical cancer | NCT01902966 | Active, not recruiting Metformin | Immunotherapy (nivolumab, pembrolizumab, sintilimab) | NSCLC, SCLC, melanoma, solid tumors | NCT03048500 ; NCT03311308 ; NCT03874000 ; NCT03874000 | Recruiting NCT02145559 | Completed Targeted therapy (temsirolimus, vandetanib, sirolimus, lapatinib …

Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

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… . | Trastuzumab, lapatinib, neratinib, tucatinib, pyrotinib ALK/ ROS1 | Receptor tyrosine kinases that are physiologically involved in nervous system development and, in cancer, most often occur as oncogenic fusion kinases (e.g., EML4-ALK and ROS1 fusions), leading to constitutive activation of the RAS … Lapatinib , also a 4-anilinoquinazoline, was designed as a dual EGFR/HER2 inhibitor; its extended aryloxy substituent increases HER2 affinity and allows clinical use in HER2-overexpressing breast cancer [ 56 , 60 , 61 ]. …

Novel Indications for Bruton's Tyrosine Kinase Inhibitors, beyond Hematological Malignancies.

Bruton's tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in p

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… Ibrutinib impacted HER2+ breast cancer cell viability at lower concentrations than the already approved HER2 TKI lapatinib [ 31 ]. …

Antibody-Drug Conjugates for Cancer Therapy.

Antibody-drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each co

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… The pivotal phase III EMELIA trial which led to FDA approval of T-DM1 in 2013 showed an improved mPFS of 9.6 months with T-DM1 vs. 6 months with lapatinib plus capecitabine (HR 0.65, 95% CI 0.55–0.77; p < 0.001) and median overall survival (mOS) of 30.9 vs. 25.1 months (HR 0.68, 95% CI 0.55–0.85; p < … T-DM1 with osimertinib is being evaluated in EGFR mutant lung cancer ( NCT03784599 ) and T-DM1 monotherapy is being tested in advanced ErbB2-positive colorectal cancer patients progressing after trastuzumab and lapatinib ( NCT03418558 ). 4.3. …

The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.

One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine parac

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… Other HER2-targeting TKIs, such as lapatinib, provide an option for patients who develop resistance to trastuzumab. … Inspired by the binding mechanism of lapatinib to EGFR, several novel formononetin compounds were designed and synthesized. …

The Impact of Monoclonal Antibody Usage on Hearing Outcomes: A Systematic Review.

ObjectiveTo ascertain trends in ototoxicity observed with monoclonal antibodies (mABs) and understand the impact they may have on hearing function.Data sourcesPubMed, Embase, Scopus.Review methodsA systematic review was performed following PRISMA guidelines. Data were reviewed for demographics, utilized mABs with respective indication and dosing, audiometric outcomes, and treatment for otologic effects.ResultsOf 757 studies reviewed, a total of 44 were included, encompassing 18,046 patients treated with mABs. Mean age of the sample was 57.8 years old. The search yielded 18 agents of ototoxicit

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… Evaluation of lapatinib and trastuzumab for ototoxic effects. J Int Adv Otol. 2015;11(3):207‐211. 10.5152/iao.2015.912. 58. Horizon Therapeutics . Tepezza prescribing information. Accessed August 5, 2024. https://www.hzndocs.com/TEPEZZA-Prescribing-Information.pdf . 59. …

Antitumoral Agent-Induced Constipation: A Systematic Review.

BackgroundConstipation is a common symptom in patients receiving antitumoral treatment. The mechanisms underlying antitumoral agent-induced constipation (ATAIC) are poorly defined. This systematic review aimed to analyze and synthesize the available information related to the prevalence, etiology, and treatment of ATAIC.MethodsA systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted. The review included human studies written in English, French, or Spanish involving patients with cancer and containing information abou

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… study | Chemotherapy | Leukemia, lymphomas, or breast cancer | 26 | Grade 1: 15.4% Grade 2: 26.9% Grade 3: 7.7% Grade 4: 7.7% Janz et al., USA, 2007 [ 31 ] | Survey | Chemotherapy and hormonotherapy | Stage 0–II breast cancer | 1372 | 30% Widakowich et al., Belgium, 2007 [ 28 ] | Narrative review | Lapatinib …

Recent Advances in Serum Biomarkers for Risk Stratification and Patient Management in Cardio-Oncology.

PURPOSE OF REVIEW: Following significant advancements in cancer therapeutics and survival, the risk of cancer therapy-related cardiotoxicity (CTRC) is increasingly recognized. With ongoing efforts to reduce cardiovascular morbidity and mortality in cancer patients and survivors, cardiac biomarkers have been studied for both risk stratification and monitoring during and after therapy to detect subclinical disease. This article will review the utility for biomarker use throughout the cancer care continuum. RECENT FINDINGS: A recent meta-analysis shows utility for troponin in monitoring patients

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… HER2 inhibitors (trastuzumab, pertuzumab, lapatinib, neratinib) are the cornerstone for treatment. The cardiotoxic effects of HER2 antagonists are likely due to interruption of HER2 signaling on the cardiomyocyte, whose normal function appears to be integral to healthy cardiac adaptation [ 69 ]. …

Biological and clinical aspects of HPV-related cancers.

Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly

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… Moreover, amplifications in PD-L1 and PD-L2 , and the BCAR4 long non-coding RNA which has previously been linked to respond to the chemotherapy drug lapatinib, an EGFR/HER2 inhibitor, have also been observed 59 . …

A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.

The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic r

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… Drugs like figitumumab and lapatinib affect the transcriptional activity of the estrogen-related receptor alpha while targeting the insulin-like growth factor (IGF) and epidermal growth factor (EGF) pathways [ 34 ]. This mechanism leads to programmed cell death in oncological targets. … Further transcriptomic studies can effectively predict resistance to figitumumab and lapatinib. Hence, omics can play an important role in drug development in these drug categories. …

Cancer treatment-related cardiotoxicity, molecular mechanism, challenges, and research trends.

Cancer treatment-related cardiotoxicity (CTRC) encompasses a spectrum of cardiovascular complications associated with chemotherapy, targeted therapy, and radiotherapy. This review synthesizes recent mechanistic insights to delineate distinct pathological pathways: anthracyclines provoke oxidative mitochondrial damage and disrupt cardiomyocyte iron homeostasis; HER2-targeted therapies inhibit the PI3K-Akt survival pathway, compromising contractile function and calcium regulation; tyrosine kinase inhibitors impair VEGF and PDGF signaling, inducing endothelial dysfunction and microvascular rarefa

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… Clinically relevant examples include proteasome inhibitors such as bortezomib for multiple myeloma and epidermal growth factor receptor (EGFR) inhibitors like lapatinib for breast cancer, both of which have demonstrated potential cardiotoxic effects [ 73 , 74 ]. …

Immune infiltration related PRDX4 facilitates the malignant features and drug resistance of breast cancer.

The incidence of breast cancer continues to increase annually, posing a significant challenge for countries worldwide in terms of its prevention and treatment. Therefore, identifying novel therapeutic targets for breast cancer is urgently needed. The peroxiredoxin (PRDX) family is regarded as a good diagnostic marker for various tumors. However, the expression and prognostic significance of PRDX family members in breast cancer remain unclear and require systematic investigation. By using bioinformatic tools such as UALCAN, TIMER2.0, Human Protein Atlas Project (HPA), Gene Set Cancer Analysis (

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… PI3K PROTAC overcomes the lapatinib resistance in PIK3CA-mutant HER2 positive breast cancer. Cancer Lett. 598 , 217112 (2024). 58. Fujii, J., Ochi, H. & Yamada, S. …

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review.

Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunothera

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… A retrospective study of HER-2-directed therapy, including trastuzumab, pertuzumab, or lapatinib, suggested sustained response to these agents among nine patients with HER-2 mutated gallbladder cancer. …

Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term wi

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… include RDV ( 101 ), with the partner drug being arbidol, BAY-2402234, brequinar, budesonide, camostat, cepharanthine, cilostazol, clobetasol, clofazimine, cobicistat, conivaptan, dabrafenib, diltiazem, drosiprenone, emetine, ezetimibe, interferon alpha, imino sugars, IQ-1S, ivermectin, ivosidenib, lapatinib … Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro. bioRxiv 77. …

Glioma drug development benefits from emerging phase 0 and window-of-opportunity trial paradigm.

Clinical drug development is fundamentally difficult for rare and difficult-to-treat solid tumors, for example, glioma. Glioblastoma (GBM), an invariably fatal primary brain tumor, poses a significant challenge in the realm of effective treatments, necessitating an accelerated approach to innovative drug discovery. Investigators keep requiring a process toward obtaining more reliable early-stage signals related to drug activity and a process toward translating those signals into clinical benefits efficiently in late-stage drug development. Besides, these processes could increase the likelihood

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… Antiproliferative effect of lapatinib in HER2-Positive and HER2-Negative/HER3-High breast cancer: results of the presurgical randomized MAPLE trial (CRUK E/06/039). Clin Cancer Res. 2015;21:2932–40. 20. Smith I, Robertson J, Kilburn L, et al. …

Ten tips for an onco-nephrology clinic.

An increasing number of cancer patients are benefiting from long term cancer-directed therapy with an ever-expanding arsenal of novel agents from monoclonal antibodies to small molecules and cellular therapies in addition to the mainstay cytotoxic chemotherapy. All these therapies are accompanied by a unique array of adverse events, which include kidney toxicity. In this context, the need for onco-nephrology expertise continues to grow. Oncologists and hematologists collaborate closely with onco-nephrologists to determine: (i) treatment options for special populations based on accurate assessm

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… ribociclib | small molecule inhibitor: CDK 4/6 | Cell-cycle arrest | OCT-2 MATE-1 MATE-2k | § ATI § AIN olaparib niraparib b rucaparib talazoparib | small molecule inhibitor: PARP | Induces cell death via tumor DNA damage | MATE-1 MATE-2k OCT-1 OCT-2 | § hemodynamic AKI suspected for niraparib tucatinib lapatinib …

Nephrotoxicity of recent anti-cancer agents.

Cancer patients may develop a variety of kidney lesions that impair not only their immediate survival but also limit the adequate treatment of the underlying malignant process. This review summarizes the nephrotoxic potential of some of the most recently developed anti-cancer drugs, focusing on those interfering with the vascular endothelial growth factor and epidermal growth factor receptor pathways and mammalian target of rapamycin inhibitors. Thrombotic microangiopathy (haemolytic-uraemic syndrome), proteinuria, hypertension and magnesium depletion are the most common side effects. Also the

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… Several other compounds were developed that have broad anti-HER activity like lapatinib ( GW572016 ), pertuzumab (2C4) and canertinib (CI-1033). …

Rare Diseases of the Orbit.

This article provides an overview of rare orbital diseases. Congenital malformations, inflammatory diseases, benign and malignant neoplasias are described. Although it represents a relatively small area of the body the orbit contains multiple different tissues. Therefore, a great variety of diseases can be found within the orbital space. That is the reason, why both the completeness and the level of detail in the description of particular diseases must be somewhat limited. Nevertheless, clinical manifestations, important aspects of diagnosis, treatment strategies, and, when specific data are a

Воздействие иммунотерапии рака на рождаемость: уделение особого внимания гематологическим заболеваниям.

В последние годы лечению раковых заболеваний способствовали новые эффективные методы лечения, включая иммунную терапию. Хотя эта терапия повышает показатели выживаемости рака, она может изменять иммунную реакцию и вызывать долгосрочные побочные эффекты, гонадотоксичные последствия и потенциальное воздействие на фертильность мужчин и женщин вызывают все большую озабоченность. Иммунотерапии, такие, как ингибиторы иммунной системы, иммуномодуляторы, моноклонные антитела и CAR-T, могут привести к повышению уровней проинфламмации цитокинов и связанных с иммунным иммунитетом неблагоприятных явлений,

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… Trastuzumab’s safety for ovarian function is further supported by data from the ALTTO study [ NCT00490139 ], which showed that adding trastuzumab to a treatment combination of lapatinib and cytotoxic chemotherapy did not raise the incidence of treatment-related amenorrhea in breast cancer patients. …