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Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications.

Cardio-oncology is an emerging field that seeks to enhance quality of life and longevity of cancer survivors. It is pertinent for clinicians to understand the cellular mechanisms of prescribed therapies, as this contributes to robust understanding of complex treatments and off-target effects, improved communication with patients, and guides long term care with the goal to minimise or prevent cardiovascular complications. Our aim is to review the cellular mechanisms of cardiotoxicity involved in commonly used anti-cancer treatments and identify gaps in literature and strategies to mitigate card

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… Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC CTG MA. J Clin Oncol. (2015) 33(14):1574–83. 10.1200/JCO.2014.56.9590 59. Mirzoeva OK, Das D, Heiser LM, Bhattacharya S, Siwak D, Gendelman R, et al. …

In vitro models of breast cancer bone metastasis: analyzing drug resistance through the lens of the microenvironment.

Even though breast cancers usually have a good outcome compared to other tumors, the cancer can progress and create metastases in different parts of the organism, the bone being a predilection locus. These metastases are usually the cause of death, as they are mostly resistant to treatments. This resistance can be caused by intrinsic properties of the tumor, such as its heterogeneity, but it can also be due to the protective role of the microenvironment. By activating signaling pathways protecting cancer cells when exposed to chemotherapy, contributing to their ability to reach dormancy, or ev

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… emtansine without the extremely harmful side effects | cardiotoxic, lung and liver issues | FDA approved for advanced or metastatic Nerlynx | Neratinib | irreversible pan-HER chemical inhibitor | Inhibits tumor growth | renal impairement | FDA approved with capecitabine advanced or metastatic Tykerb | Lapatinib …

T-Cell-Based Cellular Immunotherapy of Multiple Myeloma: Current Developments.

T-cell-based cellular therapy was first approved in lymphoid malignancies (B-cell acute lymphoblastic leukemia and large B-cell lymphoma) and expanding its investigation and application both in hematological and non-hematological malignancies. Two anti-BCMA (B cell maturation antigen) CAR (Chimeric Antigen Receptor) T-cell therapies have been recently approved for relapsed and refractory multiple myeloma with excellent efficacy even in the heavily pre-treated patient population. This new therapeutic approach significantly changes our practice; however, there is still room for further investiga

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… Tumor-Infiltrating Lymphocytes and Associations with Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated with Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial. …

Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures.

Chemotherapy and targeted therapy have opened new avenues in clinical oncology. However, there is a lack of response in a substantial percentage of cancer patients and diseases frequently relapse in those who even initially respond. Resistance is, at present, the major barrier to conquering cancer, the most lethal age-related pathology. Identification of mechanisms underlying resistance and development of effective strategies to circumvent treatment pitfalls thereby improving clinical outcomes remain overarching tasks for scientists and clinicians. Growing bodies of data indicate that stromal

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… 76 In TNBCs, CAF-released HGF improves survival of breast cancer cells in the presence of EGFR inhibitors gefitinib and erlotinib. 77 In Her2-positive breast cancers, HGF is able to restore PI3K and Ras/Raf/MEK/ERK pathway activities that were lost upon treatment with the EGFR/Her2 kinase inhibitor lapatinib …

Emerging and underexplored ginsenosides in cancer therapy (2020-2025): Beyond cytotoxic mechanisms.

Ginsenosides from Panax plants have long been studied as potential anticancer agents. In earlier years, most research focused on a few well-known ginsenosides that showed strong direct cytotoxicity, such as Rg3 and Rh2. As a result, many other ginsenosides were considered less active and received limited attention. However, studies published between 2020 and 2025 indicate that several previously underexplored ginsenosides also exhibit meaningful anticancer activity. These compounds often do not function as strongly cytotoxic agents. Instead, they act through broader and more indirect mechanism

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… Amino acid modified OCMC-g-Suc-beta-CD nanohydrogels carrying lapatinib and ginsenoside Rg1 exhibit high anticancer activity in a zebrafish model. Front Pharmacol. 2023;14 doi: 10.3389/fphar.2023.1149191. 85. …

Analysis of medical malpractice liability disputes related to novel antineoplastic drugs and research on risk prevention and control strategies.

OBJECTIVE: To investigate the general characteristics of litigation cases of medical malpractice liability disputes (MMLDs) related to novel antineoplastic drugs (NADs), the drugs involved, as well as the common types of medical errors related to NADs and their damages in the process of diagnosis and treatment, with the aims of improving the level of rational medication use in the clinical application of NADs and actively prevent medical disputes. METHODS: The China Judgments Online was searched for the cause of action using the key word "MMLDs" along with the name of 77 kinds of NADs. A tota

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… Niraparib; Olaparib; Pamiparib | 4 RET inhibitors | Pralsetinib | 1 FLT3 /AXL inhibitors | Gilteritinib | 1 Multi-targeting TKIs | Anlotinib (VEGFR/FGFR/PDGFR/KIT); Apatinib * (VEGFR2/STAT3/PD-L1 /ROS/Nrf2/p62); Avapritinib (PDGFRA/KIT); Axitinib (VEGFR/PDGFR/KIT); Donafenib; Fruquintinib (VEGFR); Lapatinib …

Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistan

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… taletrectinib BRAF fusion | 1% of sporadic PTC | Vemurafenib, dabrafenib CRC | KRAS/NRAS mutations | 35–40% of metastatic CRC patients | Not available | 45 BRAF V600E | 5–10% of metastatic CRC patients | Encorafenib+cetuximab BRCA | HER2 overexpression | ∼15% of breast cancer patients | Pertuzmab, trastuzumab, lapatinib … (e.g., ex19del, L858R) | Preclinical only | 149 AZD9291 | T790M | Cases reported * | 150 Selpercatinib Pralsetinib | RET fusions | Cases reported * | 84 AXL overexpression/amplification | NSCLC | Erlotinib | EGFR ex19del | Preclinical only | 151 Osimertinib | EGFR T790M | Preclinical only | BRCA | Lapatinib …

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

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… Analysis through a bioinformatical virtual docking system suggested that nelfinavir can potentially bind at the ATP binding site of the EGFR (ERBB1) protein, which was structurally compared with the same-site binding of the EGFR inhibitor lapatinib [ 16 ]. …

A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed.

Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with loca

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… This cascade reaction can be inhibited at different levels, with Bevacizumab targeting vascular endothelial growth factor, Ramucirumab targeting vascular endothelial growth factor receptor-2, and TKI (cabozantinib, lapatinib, and sorafenib, to mention a few) targeting post-receptor signaling pathways …

The Proliferative and Apoptotic Landscape of Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is an aggressive molecular subtype that represents up to 15% of breast cancers. It occurs in younger patients, and typically shows rapid development of locoregional and distant metastasis, resulting in a relatively high mortality rate. Its defining features are that it is positive for basal cytokeratins and, epidermal growth factor receptor and/or c-Kit. Problematically, it is typically negative for the estrogen receptor and human epidermal growth factor receptor 2 (HER2), which means that it is unsuitable for either hormone therapy or targeted HER2 therapy. As

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

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… Significant evidence shows that East Asian patients exhibit a greater response and improved survival outcomes to erlotinib, gefitinib, lapatinib, and regorafenib compared to individuals who are non‐East Asian. 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 As of now, no specific studies regarding inter‐ethnicity …

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science.

Traditional Chinese medicine (TCM) has been practiced for thousands of years and at the present time is widely accepted as an alternative treatment for cancer. In this review, we sought to summarize the molecular and cellular mechanisms underlying the chemopreventive and therapeutic activity of TCM, especially that of the Chinese herbal medicine-derived phytochemicals curcumin, resveratrol, and berberine. Numerous genes have been reported to be involved when using TCM treatments and so we have selectively highlighted the role of a number of oncogene and tumor suppressor genes in TCM therapy. I

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… Berberine reverses lapatinib resistance of HER2‐positive breast cancer cells by increasing the level of ROS . Cancer Biol Ther . 2016 ; 17 : 925 ‐ 934 . 27416292 10.1080/15384047.2016.1210728 PMC5036410 65 Kalaiarasi A , Anusha C , Sankar R , et al. …

Abstracts of the 28th Annual San Antonio Breast Cancer Symposium, December 8-11, 2005, San Antonio, Texas, USA.

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A new era of cancer immunotherapy: vaccines and miRNAs.

Cancer immunotherapy has transformed the treatment landscape, introducing new strategies to fight various types of cancer. This review examines the important role of vaccines in cancer therapy, focusing on recent advancements such as dendritic cell vaccines, mRNA vaccines, and viral vector-based approaches. The relationship between cancer and the immune system highlights the importance of vaccines as therapeutic tools. The discussion covers tumor cell and dendritic cell vaccines, protein/peptide vaccines, and nucleic acid vaccines (including DNA, RNA, or viral vector-based), with a focus on th

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… Studies have shown that miR-4728 can contribute to resistance against HER2 inhibitors like lapatinib by downregulating NOXA expression through reduced ESR1 transcription, with pharmacological inhibition of MCL-1 emerging as a potential strategy to overcome this resistance [ 130 ]. …

Chemokines: humble yet mighty players in the tumour microenvironment.

Chemokines are tiny chemotactic cytokines which play a crucial role in pathophysiology by maintaining homeostasis and inflammation. Their role in the tumour microenvironment is very much puzzling because of both pro- and anti-tumourigenic effects. Chemokines have gained much attention today, since it has been recognized that they are game changers in the TME via controlling immune cell recruitment, angiogenesis, metastasis, tumour growth and drug resistance. In this review, we are exploring the role of several chemokines and their receptors in the TME with special focus on immune cell recruitm

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… Tamoxifen, fulvestrants and aromatase inhibitors are some of the approved hormonal therapeutic agents used for the treatment of ER + BCs; correspondingly, trastuzumab, lapatinib and pertuzumab are potential HER2 targeted agents ( 108 ). …

Immunotherapy for precision medicine in colorectal cancer.

IntroductionColorectal cancer (CRC) is the fourth most common cancer and second leading cause of cancer-related death in the United States. The implementation of CRC screening has decreased CRC incidence in adults older than 65 years. However, among young adults who experience more aggressive disease progression, CRC incidence has been increasing for decades. Immunotherapy represents a collection of innovative and promising approaches with greater efficacy and safety. In this review, we discuss modalities and selected targets of immunotherapies for CRCs that are guided by precision medicine.Ar

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… Sartore-Bianchi A , Trusolino L , Martino C , Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial . …

Molecular Targeting of the BRAF Proto-Oncogene/Mitogen-Activated Protein Kinase (MAPK) Pathway across Cancers.

The mitogen-activated protein kinase (MAPK) pathway is essential for cellular proliferation, growth, and survival. Constitutive activation of this pathway by BRAF mutations can cause downstream activation of kinases, leading to uncontrolled cellular growth and carcinogenesis. Therefore, inhibition of BRAF and the downstream substrate MEK has been shown to be effective in controlling tumor growth and proliferation. Over the last decade, several BRAF and MEK inhibitors have been investigated, ranging from primarily melanoma to various cancer types with BRAF alterations. This subsequently led to

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… Lapatinib is also being evaluated as an inhibitor of RTK to prevent an increase in their signaling at the upstream level. These approaches are still mostly in the trial phase, with benefits not yet evident in clinical practice. …

JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies.

JAK/STAT signaling pathway is one of the important regulatory signaling cascades for the myriad of cellular processes initiated by various types of ligands such as growth factors, hormones, and cytokines. The physiological processes regulated by JAK/STAT signaling are immune regulation, cell proliferation, cell survival, apoptosis and hematopoiesis of myeloid and non-myeloid cells. Dysregulation of JAK/STAT signaling is reported in various immunological disorders, hematological and other solid malignancies through various oncogenic activation mutations in receptors, downstream mediators, and a

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… The decrease in the expression of the STAT3 by EGFR inhibitors such as Cetuximab, lapatinib, Erlotinib, and Gefitinib have shown minimal clinical activity in patients treated for OC ( Seshacharyulu et al., 2012 ). …

Critical considerations for targeting colorectal liver metastases with nanotechnology.

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspe

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… Biological small molecule inhibitors are increasingly incorporated in treatment regimens and currently include: epidermal growth factor receptor inhibitors (cetuximab and panitumumab); tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib); and vascular endothelial growth factor inhibitors ( …

Fucoidan Structure and Activity in Relation to Anti-Cancer Mechanisms.

Fucoidan is a natural derived compound found in different species of brown algae and in some animals, that has gained attention for its anticancer properties. However, the exact mechanism of action is currently unknown. Therefore, this review will address fucoidans structure, the bioavailability, and all known different pathways affected by fucoidan, in order to formulate fucoidans structure and activity in relation to its anti-cancer mechanisms. The general bioactivity of fucoidan is difficult to establish due to factors like species-related structural diversity, growth conditions, and the ex

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… The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition. Oncotarget. 2017;8:17887–17896. doi: 10.18632/oncotarget.14437. 16. Li B., Lu F., Wei X.J., Zhao R.X. Fucoidan: Structure and bioactivity. …