lapatinib / Generic mfg. 
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  • ||||||||||  Tykerb (lapatinib) / Novartis, Herceptin (trastuzumab) / Roche, Gilotrif (afatinib) / Boehringer Ingelheim
    Biomarker, Clinical, Journal:  Efficacy of Afatinib and Lapatinib Against HER2 Gene-amplified Trastuzumab-sensitive and -resistant Human Gastric Cancer Cells. (Pubmed Central) -  Nov 27, 2019   
    These results suggest that combined therapy with MEK and PI3KCA inhibitors could represent a novel and effective treatment option for HER2-amplified colorectal cancer. Afatinib could be a potential new molecular-targeted therapy for trastuzumab-sensitive and trastuzumab-resistant HER2 gene-amplified gastric cancers.
  • ||||||||||  Herceptin (trastuzumab) / Roche
    Clinical, Journal:  Targeting ERBB2 mutations in solid tumors: biological and clinical implications. (Pubmed Central) -  Nov 24, 2019   
    One patient developed secondary resistance. Sequencing of the progressing metastasis allowed the identification of the ERBB2 L869R mutation previously associated with resistance to lapatinib in vitro.These results support further clinical investigation aiming to demonstrate that ERBB2-mutational driven therapy can improve patient care irrespective of histology.
  • ||||||||||  Tykerb (lapatinib) / Novartis, pyrotinib (HTI-1001) / Jiangsu Hengrui Medicine, Nerlynx (neratinib) / Puma
    Clinical, Review, Clinical Trial,Phase I, Clinical Trial,Phase II, Journal:  Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer. (Pubmed Central) -  Nov 17, 2019   
    Currently, specific monoclonal antibodies and tyrosine kinase inhibitors (TKIs) are the two HER2 targeting strategies that have successfully improved the prognosis of patients with HER2-positive breast cancer. This paper focuses on three officially approved TKIs for HER2 breast cancer, namely, lapatinib, neratinib and pyrotinib, and systematically reviews the mechanism, safety, efficacy and resistance of these TKIs.
  • ||||||||||  Herceptin (trastuzumab) / Roche
    Journal, Cancer stem cells:  Inhibition of HER2 Enriches for Jagged1-dependent Breast Cancer Stem Cells: Role for Membrane Jagged1. (Pubmed Central) -  Nov 11, 2019   
    These results indicate that higher membrane Jagged1 expression may be used to either predict response to anti-HER2 therapy or for detection of Notch sensitive CSCs post therapy. Sequential blockade of HER2 followed by Jagged1 or Notch could be more effective than simultaneous blockade to prevent drug resistance and tumor progression.
  • ||||||||||  Zydelig (idelalisib) / Gilead
    Secreted Factors Determine Resistance to Idelalisib in Marginal Zone Lymphoma Models of Resistance (Hall B, Level 2 (Orange County Convention Center)) -  Nov 7, 2019 - Abstract #ASH2019ASH_3739;    
    Recombinant HBEGF also induced resistance to the BTK inhibitor ibrutinib in the PAR cells and in the mantle cell lymphoma SP-53 cell line...We identified treatments that might overcome resistance to idelalisib and are worth of further investigations . The two models, driven by different biologic processes, will allow the evaluation of further alternative therapeutic approaches.
  • ||||||||||  Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker:  MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) -  Nov 5, 2019   
    P3,  N=960, Recruiting, 
    These results propose mTORC1/2 inhibition as an effective treatment strategy in OCCC. Not yet recruiting --> Recruiting | Trial completion date: Mar 2024 --> Oct 2024 | Initiation date: Mar 2019 --> Oct 2019 | Trial primary completion date: Mar 2022 --> Oct 2022
  • ||||||||||  Herceptin (trastuzumab) / Roche, Nerlynx (neratinib) / Puma
    Journal:  Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2). (Pubmed Central) -  Nov 2, 2019   
    Thus, these findings indicate that coincident HER2 mutation reduces the efficacy of therapies commonly used to treat HER2-positive breast cancer, particularly in metastatic and previously HER2 inhibitor-treated patients, as well as potentially in patients scheduled for first-line treatment. Therefore, we propose that clinical studies testing the efficacy of neratinib are warranted selectively in breast cancer patients whose tumors carry both amplification and mutation of ERBB2/HER2.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Development of Brain-Penetrant EGFR Inhibitors for CNS Malignancies (Ballroom Lawn) -  Oct 29, 2019 - Abstract #SNO2019SNO_1025;    
    Importantly, JCN068 demonstrated superior efficacy—with negligible toxicity—compared to clinically available small molecule EGFR TKIs (erlotinib and lapatinib) against multiple EGFR-altered patient-derived orthotopic GBM xenografts. Due to these excellent drug-like properties, JCN068 is currently progressing towards clinical development for EGFR-activated GBM patients.
  • ||||||||||  Tykerb (lapatinib) / Novartis, gefitinib / Generic Mfg., foretinib (GSK1363089) / Exelixis
    Journal:  Combination of Selected MET and EGFR Inhibitors Decreases Melanoma Cells' Invasive Abilities. (Pubmed Central) -  Oct 28, 2019   
    Furthermore, used drugs led to reduction of proteolytic activity of examined cells. Our data support the idea that simultaneous targeting of EGFR and MET could be a promising therapeutic strategy inhibiting not only tumor cell growth but also its metastasis.
  • ||||||||||  Tykerb (lapatinib) / Novartis, Sprycel (dasatinib) / BMS, Otsuka, Inhibikase
    Journal:  A DFT study of inclusion complexes of substituted calix[n]arenes with dasatinib and lapatinib. (Pubmed Central) -  Oct 24, 2019   
    Moreover, for lapatinib, hosts 3f, 4a, 1f, 3d have the capability to generate promising complexes (>35 kcal/mol). Based on counterpoise corrected binding energies (E) and global reactivity descriptors, we anticipate that the proposed complexes can vitally be used as analogous to carrier-mediated-drug-delivery.
  • ||||||||||  Tykerb (lapatinib) / Novartis
    Biomarker, Journal, Tumor microenvironment, IO Biomarker:  Treatment-induced tumor cell apoptosis and secondary necrosis drive tumor progression in the residual tumor microenvironment through MerTK and IDO-1. (Pubmed Central) -  Oct 24, 2019   
    We report here that efferocytosis cleared apoptotic tumor cells in residual disease of lapatinib-treated HER2 mammary tumors in MMTV-Neu mice, increased immunosuppressive cytokines, myeloid-derived suppressor cells (MDSC), and regulatory T cells (Treg)...Combined inhibition of efferocytosis and IDO-1 in tumor RD decreased AC-induced and NC-induced immunosuppressive phenotypes, blocked tumor metastasis, and caused tumor regression in 60% of cases. This suggests that AC and NC promote tumor 'homeostasis' and progression via efferocytosis.
  • ||||||||||  irinotecan / Generic mfg.
    Systemic therapy for breast cancer brain metastases (Stars at Night Ballroom 3&4 - 3rd Level) -  Oct 19, 2019 - Abstract #SABCS2019SABCS_2012;    
    P2
    Finally, there is evidence that monoclonal antibodies and antibody drug conjugates may have CNS activity; for example, trastuzumab-emtansine has been reported to lead to CNS regressions in up to 40% of patients, based upon case series from several institutions, and in preliminary data from the PATRICIA study, the regimen of high dose trastuzumab (6 mg/kg weekly) plus pertuzumab was associated with CNS responses and prolonged stable disease in a subset of patients...Results of the JPBO study demonstrate modest CNS efficacy of abemaciclib in patients with ER+ breast cancer, but the CNS ORR was <10%...An ongoing randomized trial testing carboplatin +/- veliparib is asking the question of whether a PARP inhibitor may add to platinum efficacy both intracranially and extracranially...Diverse agents including anthracyclines, capecitabine, platinum salts, and irinotecan have been reported to be associated with CNS response in breast cancer patients. Newer compounds (NKTR-102, Nal-IRI, tesetaxel, ANG1005) which have been engineered to improve upon CNS penetration and/or CNS residence time are in clinical development and testing.
  • ||||||||||  Tykerb (lapatinib) / Novartis, PLX4720 / Daiichi Sankyo
    Biomarker, Journal:  Biomarker discovery by integrated joint non-negative matrix factorization and pathway signature analyses. (Pubmed Central) -  Oct 11, 2019   
    Our biomarker discovery scheme represents an integration of JNMF multi-omics clustering and multi-layer interpretation based on pathway gene signature analyses. This approach is also expected to be useful for establishing drug development strategies, identifying pharmacodynamic biomarkers, in mode of action analysis, as well as for mining drug response data in a clinical setting.
  • ||||||||||  Tykerb (lapatinib) / Novartis, Herceptin (trastuzumab) / Roche, Perjeta (pertuzumab) / Roche
    Journal:  Trastuzumab Plus Pertuzumab Resistance Does Not Preclude Response to Lapatinib Plus Trastuzumab in HER2-Amplified Colorectal Cancer. (Pubmed Central) -  Oct 10, 2019   
    Although clinical trials have reported activity for trastuzumab/pertuzumab and trastuzumab/lapatinib combinations, there are no reports on lapatinib plus trastuzumab activity after resistance to trastuzumab plus pertuzumab. Presented are three cases of HER2 amplified colorectal cancer that developed acquired refractoriness to trastuzumab pertuzumab with subsequent clinical benefit to lapatinib plus trastuzumab, highlighting the potential for HER2 tyrosine kinase inhibition plus trastuzumab in overcoming trastuzumab/pertuzumab resistance.
  • ||||||||||  RRx-001 / EpicentRx, Stivarga (regorafenib) / Bayer, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
    In Vitro and In Vivo RRx-001 Synergy with Regorafenib and In Vivo Attenuation of Regorafenib-Induced Toxicity (Prince George's Exhibition Halls AB) -  Oct 2, 2019 - Abstract #SITC2019SITC_863;    
    A clinical trial is planned to investigate the translational potential of the RRx-001 + regorafenib combination. Future experiments will determine whether RRx-001 also enhances the activity and decreases the toxicity of other tyrosine kinase inhibitors such as sorafenib, sunitinib, dasatinib, imatinib, lapatinib, and cabozantinib, all of which possess similar efficacy and safety profiles, not only in colorectal cancer but also other tumor types.
  • ||||||||||  lapatinib / Generic mfg.
    Journal:  Th1 cytokines sensitize HER-expressing breast cancer cells to lapatinib. (Pubmed Central) -  Oct 2, 2019   
    Interestingly, when lapatinib resistant lines MDA-MB-453 and JIMT-1 were tested, it was found that the presence of Th1 cytokines appeared to enhance sensitivity for lapatinib-induced metabolic suppression and induction of apoptotic cell death, nearly abrogating drug resistance. These studies provide pre-clinical data suggesting the possibility that targeted drug therapy may be combined with vaccination to enhance anti-cancer effects, and furthermore that robust immunity in the form of secreted Th1 cytokines may have the capacity to mitigate resistance to targeted drugs.