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Negative Regulation of Cell Adhesion as a Driver of Brain Metastasis in NSCLC Patients with EGFR Amplification.

Brain metastases are strongly associated with a poor prognosis. Experimental animal models have provided valuable insights into the complex biology underlying brain metastasis, and translating these findings could pave the way for innovative management strategies for patients with brain metastases. Between May 2019 and June 2023, twenty-four lung cancer patients and thirty patients with brain metastases from lung cancer were enrolled at Guangdong Sanjiu Brain Hospital. Next-generation targeted panel sequencing (NGS) was performed on lung cancer tissue and surgical specimens from brain tumors f

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… Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. J Natl Cancer Inst. 2008;100(15):1092–103. 8. Gállego Pérez-Larraya J, Hildebrand J. Brain metastases. Handb Clin Neurol. 2014;121:1143-57. 9. …

Mapping the EORTC QLQ-C30 to EQ-5D-3L in patients with breast cancer.

BackgroundThe types of outcomes measured collected in clinical studies and those required for cost-effectiveness analysis often differ. Decision makers routinely use quality adjusted life years (QALYs) to compare the benefits and costs of treatments across different diseases and treatments using a common metric. QALYs can be calculated using preference-based measures (PBMs) such as EQ-5D-3L, but clinical studies often focus on objective clinician or laboratory measured outcomes and non-preference-based patient outcomes, such as QLQ-C30. We model the relationship between the generic, preference

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… Eligible patients were adults who had HER2-positive, recurrent or unresectable locally advanced breast cancer or metastatic breast cancer and had previously received taxane therapy in any setting or more than one HER2-directed regimens in an advanced setting; these included trastuzumab and lapatinib. …

Characteristics of clinical trials in rare vs. common diseases: A register-based Latvian study.

BackgroundConducting clinical studies in small populations may be very challenging; therefore quality of clinical evidence may differ between rare and non-rare disease therapies.ObjectiveThis register-based study aims to evaluate the characteristics of clinical trials in rare diseases conducted in Latvia and compare them with clinical trials in more common conditions.MethodsThe EU Clinical Trials Register (clinicaltrialsregister.eu) was used to identify interventional clinical trials related to rare diseases (n = 51) and to compose a control group of clinical trials in non-rare diseases (n = 1

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… Obinutuzumab (Gazyvaro) | CLL | Phase III, open label | | AE | 55 | 7 | 560 | 800 Eltrombopag (Revolade) | ITP | Phase II, RCT, double blind | Placebo | Platelet count | 18 | 10 | 129 | 422 Dinaciclib (SCH-727965) | CLL | Phase III, RCT, open label | Ofatumumab (Arzerra) | PFS | 38 | 8 | 225 | 466 Lapatinib …

Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.

BackgroundZalypsis(®) is a marine compound in phase II clinical trials for multiple myeloma, cervical and endometrial cancer, and Ewing's sarcoma. However, the determinants of the response to Zalypsis are not well known. The identification of biomarkers for Zalypsis activity would also contribute to broaden the spectrum of tumors by selecting those patients more likely to respond to this therapy.MethodsUsing in vitro drug sensitivity data coupled with a set of molecular data from a panel of sarcoma cell lines, we developed molecular signatures that predict sensitivity to Zalypsis. We verified

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… In contrast, gefitinib, erlotinib, and lapatinib are more specific for the EGFR family. We propose the use of a specific tyrosine kinase inhibitor according to the RTK active in the patient’s tumor, thus promoting personalized treatment. …

Update on Classic and Novel Approaches in Metastatic Triple-Negative Breast Cancer Treatment: A Comprehensive Review.

Triple-negative breast cancer (TNBC) accounts for almost 15% of all diagnosed breast cancers and often presents high rates of relapses and metastases, with generally poor prognosis despite multiple lines of treatment. Immunotherapy has radically changed the approach of clinicians towards TNBC in the last two to three years, even if targeted and specific therapeutic options are still missing; this unmet need is further justified by the extreme molecular and clinical heterogeneity of this subtype of breast cancer and by the weak response to both single-agent and combined therapies. In March 2023

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… This oral agent was initially approved in anthracycline and taxane-resistant breast cancer and subsequently approved for use in combination with docetaxel as second-line therapy in metastatic BC, or in combination with small-molecule lapatinib in women with human epidermal growth factor receptor type … Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer N. Engl. J. Med. 2006 355 2733 2743 10.1056/NEJMoa064320 17192538 33. Park I.H. Im S.-A. Jung K.H. Sohn J.H. Park Y.H. Lee K.S. Sim S.H. Park K.-H. Kim J.H. Nam B.H. …

Antibody-Drug Conjugates: Ushering in a New Era of Cancer Therapy.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancer, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development. The therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refract

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… . | T-DM1: 495 Capecitabine + lapatinib: 496 | Ab target: HER2 Linker: SMCC (non-cleavable) Payload: DM1 | ORR 43.6% vs. 30.8%, mPFS 9.6 vs. 6.4 mths, mOS 30.9 vs. 25.1 mths. 2019 | KATHERINE [ 65 ] (phase III) | Early-stage HER2+ breast cancer with residual disease after NACT. | T-DM1: 743 Trastuzumab … It has been shown to improve median overall survival in patients with metastatic HER2-positive breast cancer treated in the second-line setting compared to capecitabine plus lapatinib, with a hazard ratio of 0.68 (95% CI 0.55 to 0.85, p < 0.001) [ 64 ]. …

Exploiting Nanomedicine for Cancer Polychemotherapy: Recent Advances and Clinical Applications.

The most important limitations of chemotherapeutic agents are severe side effects and the development of multi-drug resistance. Recently, the clinical successes achieved with immunotherapy have revolutionized the treatment of several advanced-stage malignancies, but most patients do not respond and many of them develop immune-related adverse events. Loading synergistic combinations of different anti-tumor drugs in nanocarriers may enhance their efficacy and reduce life-threatening toxicities. Thereafter, nanomedicines may synergize with pharmacological, immunological, and physical combined tre

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… In order to enhance the cytotoxic properties of DOX and overcome MDR, Wang H et al. [ 52 ] used poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonylpropylene carbonate)-based NP containing DOX and lapatinib, a kinase inhibitor, in order to treat the drug-resistant breast cancer induced with MCF … Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer Mol. Pharm. 2014 11 2600 2611 10.1021/mp400687w 24405470 53. Cohen S.M. Mukerji R. Cai S. Damjanov I. Forrest M.L. Cohen M.S. …

Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges.

Gastrointestinal (GI) cancer remains the deadliest cancer in the world. The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery, and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer. There is well-established evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies, which should routinely be incorporated into treatment strategies for GI cancer. Other potential therapeutic targets involve the PI3K/AKT pathwa

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… Dual HER2 inhibition with trastuzumab and lapatinib in patients with HER2-amplified, KRAS wild-type metastatic CRC who are resistant to standard therapies, including EGFR-targeted agents, demonstrated that dual HER2 blockade can produce objective responses[ 23 ]. … Bergamo F Zagonel V Leone F Depetris I Martinelli E Troiani T Ciardiello F Racca P Bertotti A Siravegna G Torri V Amatu A Ghezzi S Marrapese G Palmeri L Valtorta E Cassingena A Lauricella C Vanzulli A Regge D Veronese S Comoglio PM Bardelli A Marsoni S Siena S Dual-targeted therapy with trastuzumab and lapatinib …

The Roadmap of RANKL/RANK Pathway in Cancer.

The receptor activator of the nuclear factor-κB ligand (RANKL)/RANK signaling pathway was identified in the late 1990s and is the key mediator of bone remodeling. Targeting RANKL with the antibody denosumab is part of the standard of care for bone loss diseases, including bone metastases (BM). Over the last decade, evidence has implicated RANKL/RANK pathway in hormone and HER2-driven breast carcinogenesis and in the acquisition of molecular and phenotypic traits associated with breast cancer (BCa) aggressiveness and poor prognosis. This marked a new era in the research of the therapeutic use o

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… In this study, it was shown that RANKL stimulation increased NF-κB activation in lapatinib-resistant HER2+ cell lines compared to their sensitive counterparts, whereas RANK loss sensitized lapatinib-resistant cells to the drug in vitro. …

The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles publ

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… The combination of the lysosome disruptor siramesine and the tyrosine kinase inhibitor lapatinib increased the expression of TF and reduced the expression of FPN1 in breast cancer cells, thereby promoting iron overload in the lysosome and ultimately inducing ferroptosis ( Ma et al., 2016 ). … Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis. 7 (7), e2307. 10.1038/cddis.2016.208 Malfa G. A., Tomasello B., Acquaviva R., Genovese C., La Mantia A., Cammarata F. P., et al. (2019). Betula etnensis raf. …

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy.

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy reg

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… . | Drug | Category | Mechanism of Anticancer Action | Type of Cardiotoxicity | Cancers Treated 1 | Trastuzumab, Pertuzumab | Monoclonal Antibodies | HER2 inhibitors | LVSD, heart failure, orthostatic hypotension | Metastatic colorectal cancer, lung cancer, malignancies, myeloma [ 22 ] 2 | Lapatinib, … In this review, the different anticancer drugs used in CRC chemotherapy, which induce cardiotoxicity, include trastuzumab, pertuzumab (monoclonal antibodies), lapatinib, sunitinib, pazopanib, sorafenib, imatinib, dasatinib, nilotinib, bosutinib, ponatinib (tyrosine kinase inhibitor), cyclophosphamide …

Thirteen-year analyses of medical oncology outpatient day clinic data: a changing field.

BackgroundNovel treatment modalities like targeted therapy and immunotherapy are currently changing treatment strategies and protocols in the field of medical oncology.MethodsNumbers of patients and patient contacts admitted to medical oncology day clinics of a large European academic cancer centre in the period from 2006 to 2018 were analysed using our patient administration system.ResultsA patient cohort of 9.870 consecutive individual patients with 125.679 patient contacts was descriptively and retrospectively characterised. Mean age was 59.9 years. A substantial increase in both individual

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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. …

Keyword Index for Volume 110

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… 1785 keratinocyte 199 Ki-67 1561, 2847 Ki67 promoter 2496 kidney cancer 1622 kinase and phosphatase inhibitors 2441 KIT 1155 KLF17 1298 KLF4 450 K–PD modelling 1517 K-RAS 648, 1606, 2047 2874 KRAS gene mutation 1148 lactate dehydrogenase inhibitors 172 laparoscopic radical cystectomy 842 lapatinib …

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving

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… Upregulated glutamine metabolism and reactivated mTOR signaling have been shown to cause resistance to HER2-targeted therapies such as lapatinib [ 96 ]. …

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

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… Lapatinib and neratinib, which are clinically available for patients with breast cancer, are dual-target inhibitors that inhibit the activities of both EGFR and HER2 (Table 1 ). … Among them, lapatinib is a reversible TKI and is mainly used in combination with capecitabine for the treatment of advanced or metastatic breast cancers that show HER2 overexpression and have previously received treatment by anthracycline, paclitaxel, or Herceptin. 85 Neratinib is an irreversible inhibitor …

Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.

Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway - has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequ

Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies.

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored

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… Among 991 patients, T‐DM1 showed a median progression‐free survival (PFS) of 9.6 versus 6.4 months for lapatinib plus capecitabine, and a median OS of 30.9 versus 25.1 months, respectively. … The rate of grade 3 or 4 adverse events was lower with T‐DM1 (41%) compared with lapatinib plus capecitabine (57%). …

Comparison of the effects of zoledronic acid versus denosumab on bone metabolism, inflammatory response, and immunoglobulins in breast cancer patients with bone metastases.

BackgroundThis study aimed to compare the effects of Zoledronic Acid (ZA) versus Denosumab (DEN) on bone metabolism, inflammatory response, and immunoglobulins in breast cancer (BC) patients with bone metastases.MethodsThe potential study population consisted of 163 patients with bone metastases BC admitted from May 2023 to June 2024. Through propensity score matching (PSM), 122 patients were included, with 61 patients in the ZA group (treated with ZA) and 61 patients in the DEN group (treated with DEN). Levels of tartrate-resistant acid phosphatase 5b (TRACP-5b), bone glutamyl protein (BGP),

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… Treatment protocol For hormone receptor-positive (ER+/PR+) BC patients, endocrine therapies such as Tamoxifen and Letrozole were given; for HER2-positive BC patients, targeted therapies such as Trastuzumab and Lapatinib were given; and for hormone receptor-negative BC patients with rapid disease progression …

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 …

Assessment of Coverage in England of Cancer Drugs Qualifying for US Food and Drug Administration Accelerated Approval.

ImportanceNumerous cancer drugs have received accelerated approval from the US Food and Drug Administration (FDA) based on clinical trial outcomes that are otherwise not acceptable for traditional FDA approval; the accelerated approval process allows outcomes based on surrogate measures that are only reasonably likely to estimate clinical benefits. In England, the National Institute for Health and Care Excellence (NICE) evaluates the clinical benefits and cost-effectiveness of drugs after they have received regulatory approval and issues recommendations regarding their coverage in the National

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… Committee for Medicinal Products for Human Use Gemtuzumab | Acute myeloid leukemia | Withdrawn | Denied market authorization | Not reviewed | EMA: did not indicate benefit and was insufficient to validate effectiveness without a comparator; few patients achieved complete remission; severe adverse effects Lapatinib …