Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D03301 (PDL)
 658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A majority of non-small cell lung cancer (NSCLC), especially adenocarcinomas, harbour at least one oncogenic driver mutation that can potentially be a target for therapy. The treatment of these oncogene-addicted tumors has dramatically changed the outcome of these patients, where tyrosine kinase inhibitors (TKIs) of mutated epidermal growth factor receptor (EGFR) and rearranged anaplastic lymphoma kinase (ALK) have paved the way for a new era of precision cancer medicine. Another paradigm shift in the treatment of NSCLC, as well as numerous other tumor types, has been the introduction of immunotherapy (IO) with immune checkpoint inhibitors targeting mainly programmed cell death-1 (PD-1) or its ligand PDL-L1, where studies have demonstrated an increased survival versus standard treatment with chemotherapy, both in the first- and second-line setting. However, the role of IO in oncogene-addicted NSCLC is still unclear where most clinical data come from subgroup analyses with low number of patients in larger randomized trials, and these data do not support the use of IO after TKI in this category of NSCLC patients. The purpose of this review is to summarize the existing evidence about the use of IO in oncogenic-addicted NSCLC and highlight the issues that should be addressed in the future in order to define the role of IO for these patients.
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PMID:Oncogene-addicted non-small cell lung cancer and immunotherapy. 2995 5

The epidermal growth factor receptor (EGFR) pathway is a well-studied oncogenic pathway in human non-small cell lung cancer (NSCLC). A subset of advanced NSCLC patients (15-55%) have EGFR-driven mutations and benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). Immune checkpoint inhibitors (ICIs) targeting the PD-1/PDL-1 axis are a new anti-cancer therapy for metastatic NSCLC. The anti-PD-1/PDL-1 ICIs showed promising efficacy (~30% response rate) and improved the survival of patients with metastatic NSCLC, but the role of anti-PD-1/PDL-1 ICIs for EGFR mutant NSCLC is not clear. YAP (yes-associated protein) is the main mediator of the Hippo pathway and has been identified as promoting cancer progression, drug resistance, and metastasis in NSCLC. Here, we review recent studies that examined the correlation between the EGFR, YAP pathways, and PD-L1 and demonstrate the mechanism by which EGFR and YAP regulate PD-L1 expression in human NSCLC. About 50% of EGFR mutant NSCLC patients acquire resistance to EGFR-TKIs without known targetable secondary mutations. Targeting YAP therapy is suggested as a potential treatment for NSCLC with acquired resistance to EGFR-TKIs. Future work should focus on the efficacy of YAP inhibitors in combination with immune checkpoint PD-L1/PD-1 blockade in EGFR mutant NSCLC without targetable resistant mutations.
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PMID:Epidermal Growth Factor Receptor (EGFR) Pathway, Yes-Associated Protein (YAP) and the Regulation of Programmed Death-Ligand 1 (PD-L1) in Non-Small Cell Lung Cancer (NSCLC). 3138 56

Over the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine. The management of this breast cancer subgroup has thus been revolutionized and its prognosis has changed dramatically. Nevertheless, HER2-positive advanced breast cancer remains an incurable disease and resistance to conventional anti-HER2 drugs is almost unavoidable. Nowadays, biochemical and pharmaceutical advances are meeting the challenge of developing increasingly sophisticated therapies directed against HER2, including novel anti HER2 antibodies with increased affinity. New antibody-drug conjugates (ADC) with more advanced pharmacological properties, and dual targeting of epitopes via bispecific monoclonal antibodies are also emerging. In addition, more potent and more specific HER2 tyrosine kinase inhibitors have shown interesting outcomes and are under development. Finally, researchers' interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.
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PMID:New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?pi. 3254 95