0000000000087696
AUTHOR
Luis E. Raez
showing 16 related works from this author
Moving osimertinib to first-line: the right “strategy” in the chessboard of epidermal growth factor receptor-mutated non-small cell lung cancer?
2018
In the N Engl J Med , Soria and colleagues have recently reported the results of the phase III randomized FLAURA trial (1), comparing osimertinib with first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) gefitinib or erlotinib in treatment-naive patients with advanced non-small cell lung cancer (NSCLC) and activating EGFR -mutations.
Primary and metastatic brain cancer genomics and emerging biomarkers for immunomodulatory cancer treatment
2018
Abstract: Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' micro environment in order to predict the potential activit…
Molecular target therapy for bone metastasis : starting a new era with denosumab, a RANKL inhibitor
2014
Abstract: Introduction: The skeleton is generally the primary, and sometimes the only, site of metastasis in patients with advanced solid tumors. Bone metastases are the most frequent cause of cancer-related pain and the origin of severe morbidity in patients. Among the treatment options available for the prevention of skeletal-related events (SREs) associated with bone metastasis, zoledronic acid, an antiresorptive treatment from the group of bisphosphonates, is currently the standard of care in this setting. Areas covered: Zoledronic acid, together with denosumab (a monoclonal antibody against the receptor activator of nuclear factor kappa B ligand), is the most frequent approach for the …
The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment…
2017
Abstract: Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor n…
BIBF 1120/ nintedanib : a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer.
2013
Abstract: Introduction: Several new targeted agents with anti-angiogenic properties have been developed recently, including vandetanib, sunitinib, sorafenib, bevacizumab and others. Tumor development, progression, metastasis are strongly linked to angiogenesis. Targeted agents like bevacizumab, a monoclonal antibody which targets VEGF, have been fully developed in several solid tumors. These new agents strongly advocate that targeting angiogenesis is one of the best approaches for cancer therapy. Areas covered: Those agents that target additional pro-angiogenic intracellular signaling pathways beyond VEGF signaling have also the potential to contribute to anticancer therapies. The authors p…
Entrectinib: a potent new TRK, ROS1, and ALK inhibitor
2015
Abstract: Introduction: Receptor tyrosine kinases (RTKs) and their signaling pathways, control normal cellular processes; however, their deregulation play important roles in malignant transformation. In advanced non-small cell lung cancer (NSCLC), the recognition of oncogenic activation of specific RTKs, has led to the development of molecularly targeted agents that only benefit roughly 20% of patients. Entrectinib is a pan-TRK, ROS1 and ALK inhibitor that has shown potent anti-neoplastic activity and tolerability in various neoplastic conditions, particularly NSCLC. Areas covered: This review outlines the pharmacokinetics, pharmacodynamics, mechanism of action, safety, tolerability, pre-cl…
The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer
2016
Abstract: Introduction: Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation. Area covered: This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in e…
Second-Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological, and Molecular Aspects of Nintedanib
2017
Abstract: Lung carcinoma is the leading cause of death by cancer in the world. Nowadays, most patients will experience disease progression during or after first-line chemotherapy demonstrating the need for new, effective second-line treatments. The only approved second-line therapies for patients without targetable oncogenic drivers are docetaxel, gemcitabine, pemetrexed, and erlotinib and for patients with target-specific oncogenes afatinib, osimertinib, crizotinib, alectinib, and ceritinib. In recent years, evidence on the role of antiangiogenic agents have been established as important and effective therapeutic targets in non-small cell lung cancer (NSCLC). Nintedanib is a tyrosine kinas…
Immune checkpoint inhibitors in lung cancer: the holy grail has not yet been found…
2017
Lung cancer is rich in molecular complexities and driven by different abnormal molecular pathways. Personalised medicine has begun to bring new hope for the treatment of patients with lung cancer, especially non-small cell lung cancer (NSCLC). The development of molecularly targeted therapy (small molecules and monoclonal antibodies) has significantly improved outcomes in the metastatic setting for patients with NSCLC whose tumours harbour activated oncogenes such as epidermal growth factor receptor (EGFR) and translocated genes like anaplastic lymphoma kinase (ALK). In addition, immune checkpoint inhibitors have also dramatically changed the therapeutic landscape of NSCLC. In particular, m…
Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?
2014
Abstract: Immunotherapy has been studied for many years in lung cancer without significant results, making the majority of oncologists quite skeptical about its possible application for non-small cell lung cancer treatment. However, the recent knowledge about immune escape and subsequent cancer immunoediting has yielded the development of new strategies of cancer immunotherapy, heralding a new era of lung cancer treatment. Cancer vaccines, including both whole-cell and peptide vaccines have been tested both in early and advanced stages of non-small cell lung cancer. New immunomodulatory agents, including anti-CTLA4, anti-PD1/PDL1 monoclonal antibodies, have been investigated as monotherapy …
The role of cMET in non-small cell lung cancer resistant to EGFR-Inhibitors: Did we really find the target?
2014
Abstract: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpr…
Extracellular vesicles as miRNA nano-shuttles : dual role in tumor progression
2018
[EN] Tumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer, interacting with target cells of the tumor microenvironment, such as fibroblasts, immune and endothelial cells. EVs can modulate tumor progression, angiogenic switch, metastasis, and immune escape. These vesicles are nano-shuttles containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs contained in extracellular vesicles (EV-miRNAs) are disseminated in the extracellular space and are able to influence the expression of target genes with either tumor suppressor or oncogenic functions, depending on both parental and target cells. Metastatic cancer cells can balance their oncogenic pote…
BRAF mutations in non-small cell lung cancer : has finally Janus opened the door?
2016
Abstract: B-Raf mutations occur in about 1-2% of non-small cell lung cancers (NSCLC). These mutations generate a permanent activation of the mitogen activated protein kinase (MAPK) pathway, which promotes tumor growth and proliferation. In the present review, we discuss B-Raf mutation epidemiology, diagnostic methods to detect B-Raf mutations, the role of B-Raf as a driver mutation and a potential therapeutic target in NSCLC. The results of clinical trials involving B-Raf or MAPK pathway inhibitors for the treatment of NSCLC are also discussed. Clinical trials evaluating B-Raf inhibitors in BRAF mutated NSCLC patients have shown promising results, and larger prospective studies are warrante…
Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors
2014
Abstract: Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current…
Nintedanib in non-small cell lung cancer: from preclinical to approval
2015
Angiogenesis is a driving force of a tumor’s development. Targeting this process is an attractive option, as this is a feature shared by most of the solid tumors. A lot of antiangiogenic drugs have been developed following this path, including bevacizumab, sorafenib, sunitinib, vandetanib, ramucirumab, motesanib and many others. The latest drug of this class to be approved for patients with non-small cell lung cancer (NSCLC) was nintedanib, a triple angiokinase inhibitor. This molecule targets vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways, avoiding the tumor’s switch to normal escape mechanisms. The pharmacokine…
ALK and crizotinib: After the honeymoon...what else? Resistance mechanisms and new therapies to overcome it
2014
The last few decades have witnessed a silent revolution in the war against NSCLC, thanks to the discovery of “oncogenic drivers” and the subsequent development of targeted therapies. The discovery of the EML4-ALK fusion gene in a subgroup of patients with NSCLC and the subsequent clinical development of crizotinib has been an amazing success story in lung cancer translational-research, and its accelerated approval [only 4 years from the discovery of ALK rearrangement in NSCLC to the approval by the Food and Drug Administration (FDA)] marked the beginning of the new decade of targeted therapy. However, common to all targeted therapies, despite an initial benefit, patients inevitably experien…