Advances in anti-BRAF therapies for lung cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Roviello G
PROVIDER: S-EPMC8068629 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The amounts of eIF4G and eIF4B were decreased in the vemurafenib-treated sensitive A375 cell line. To find mechanisms behind this decrease, we sought to identify the genes whose expression changes after vemurafenib treatment in A375 cells as compared to Mel624 cells by using microarrays.
2014-12-30 | E-MTAB-2607 | biostudies-arrayexpress
Project description:Anti-fungal therapies remain sub-optimal, and resistant pathogens are increasing. New therapies are desperately needed, especially options that are less toxic than most of the currently available selection. In this review, I will discuss anti-fungal therapies that are in at least phase I human trials. These include VT-1161 and VT-1598, modified azoles with a tetrazole metal-binding group; the echinocandin rezafugin; the novel β-1,3-d-glucan synthase inhibitor ibrexafungerp; fosmanogepix, a novel anti-fungal targeting Gwt1; the arylamidine T-2307; the dihydroorotate inhibitor olorofim; and the cyclic hexapeptide ASP2397. The available data including spectrum of activity, toxicity and stage of clinical development will be discussed for each of these so clinicians are aware of promising anti-fungal agents with a strong likelihood of clinical availability in the next 5-7 years.
| S-EPMC8280599 | biostudies-literature
Project description:Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAFV600E colorectal cancer (mCRCBRAF-V600E). However, a large fraction of patients do not respond, underscoring the need to identify molecular determinants of treatment response. Using whole-exome sequencing in a discovery cohort of patients with mCRCBRAF-V600E treated with anti-BRAF/EGFR therapy, we found that inactivating mutations in RNF43, a negative regulator of WNT, predict improved response rates and survival outcomes in patients with microsatellite-stable (MSS) tumors. Analysis of an independent validation cohort confirmed the relevance of RNF43 mutations to predicting clinical benefit (72.7% versus 30.8%; P = 0.03), as well as longer progression-free survival (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.12-0.75; P = 0.01) and overall survival (HR, 0.26; 95% CI, 0.10-0.71; P = 0.008), in patients with MSS-RNF43mutated versus MSS-RNF43wild-type tumors. Microsatellite-instable tumors invariably carried a wild-type-like RNF43 genotype encoding p.G659fs and presented an intermediate response profile. We found no association of RNF43 mutations with patient outcomes in a control cohort of patients with MSS-mCRCBRAF-V600E tumors not exposed to anti-BRAF targeted therapies. Overall, our findings suggest a cross-talk between the MAPK and WNT pathways that may modulate the antitumor activity of anti-BRAF/EGFR therapy and uncover predictive biomarkers to optimize the clinical management of these patients.
| S-EPMC9556333 | biostudies-literature
Project description:Osteoporosis is a type of bone loss disease characterized by a reduction in bone mass and microarchitectural deterioration of bone tissue. With the intensification of global aging, this disease is now regarded as one of the major public health problems that often leads to unbearable pain, risk of bone fractures, and even death, causing an enormous burden at both the human and socioeconomic layers. Classic anti-osteoporosis pharmacological options include anti-resorptive and anabolic agents, whose ability to improve bone mineral density and resist bone fracture is being gradually confirmed. However, long-term or high-frequency use of these drugs may bring some side effects and adverse reactions. Therefore, an increasing number of studies are devoted to finding new pathogenesis or potential therapeutic targets of osteoporosis, and it is of great importance to comprehensively recognize osteoporosis and develop viable and efficient therapeutic approaches. In this study, we systematically reviewed literatures and clinical evidences to both mechanistically and clinically demonstrate the state-of-art advances in osteoporosis. This work will endow readers with the mechanistical advances and clinical knowledge of osteoporosis and furthermore present the most updated anti-osteoporosis therapies.
| S-EPMC10175743 | biostudies-literature
Project description:The mainstay of treatment for early-stage non-small-cell lung cancer (NSCLC) is surgical resection. Traditionally, chemotherapy has been used perioperatively in locally extensive disease to improve the oncologic outcomes of surgery, with a 5-year absolute survival benefit of approximately 5%. In recent years, immunotherapy and molecular targeted therapy have shown excellent results in the treatment of locoregionally advanced and metastatic NSCLC, replacing chemotherapy as first-line treatment in certain cases. Consequently, researchers have been increasingly investigating the use of immunotherapy or targeted therapy in combination with surgery for the treatment of early-stage disease. This growing research interest has resulted in several published and ongoing studies of various size and design. In this mini review, we provide a succinct and up-to-date overview of recently published, phase 3 randomized clinical trials on adjuvant and neoadjuvant immunotherapy or targeted therapy for NSCLC. We subsequently discuss some important unresolved clinical issues, including the optimal duration of treatment, scheduling with respect to surgery, and potential combinations of different systemic therapies. Finally, we reference large, randomized, phase 3 studies that are currently in progress and may give answers to those and other clinical questions.
| S-EPMC9895369 | biostudies-literature
Project description:Toll-like receptors (TLRs) are pattern recognition receptors, originally discovered to stimulate innate immune reactions against microbial infection. TLRs also play essential roles in bridging the innate and adaptive immune system, playing multiple roles in inflammation, autoimmune diseases, and cancer. Thanks to the immune stimulatory potential of TLRs, TLR-targeted strategies in cancer treatment have proved to be able to regulate the tumor microenvironment towards tumoricidal phenotypes. Quantities of pre-clinical studies and clinical trials using TLR-targeted strategies in treating cancer have been initiated, with some drugs already becoming part of standard care. Here we review the structure, ligand, signaling pathways, and expression of TLRs; we then provide an overview of the pre-clinical studies and an updated clinical trial watch targeting each TLR in cancer treatment; and finally, we discuss the challenges and prospects of TLR-targeted therapy.
| S-EPMC9721395 | biostudies-literature
Project description:IntroductionThere are limited data on the influence of different anti-cancer therapies on lymphocyte subpopulations and their relationships to survival of non-small cell lung cancer (NSCLC) patients. This study aimed to assess the effect of immunotherapy, chemotherapy, immunochemotherapy, adjuvant chemotherapy after surgery, and antibodies against Vascular Endothelial Growth Factors (VEGF) on B cell, T cell, and NK cell subpopulations, and the survival time of NSCLC patients.MethodsA total of 32 consecutive NSCLC patients were recruited at Pulmonology Clinic, Leipzig from January 2018 to March 2020 and enrolled in this study. Immunophenotyping was done using a FACS Canto II flow cytometer (BD Biosciences) before the administration of the planned therapy and during therapy with up to 7 observational windows for each patient targeting 130 immunologic parameters.ResultsAbsolute transitional B cells was significantly increased after immunotherapy (p = 0.032), immunochemotherapy (p = 0.030), and antibodies against VEGF (p = 0.024). Similarly, absolute counts and percentage of B cells were significantly increased after adjuvant chemotherapy (p = 0.023). However, absolute counts and percentage of transitional B cells are significantly decreased after chemotherapy (p = 0.001). Activated cytotoxic T cells were significantly increased after immunotherapy (p = 0.031) and immunochemotherapy (p = 0.030). The overall survival rate of NSCLC patients was 31%.ConclusionsIn conclusion, this study suggests that different types of anti-cancer therapies affect lymphocyte subpopulations of NSCLC patients. Further large-scale and multicentre studies are required to confirm our results and to evaluate the prognostic value of lymphocyte subpopulations.
| S-EPMC10493868 | biostudies-literature
Project description:Oncolytic adenoviruses (Onc.Ads) selectively replicate in and lyse cancer cells and are therefore commonly used vectors in clinical trials for cancer gene therapy. Building upon the well-characterized adenoviral natural tropism, genetic modification of Onc.Ad can enhance/regulate their transduction and replication within specific cancer cell types. However, Onc.Ad-mediated tumor cell lysis cannot fully eliminate tumors. The hostile tumor microenvironment provides many barriers to efficient oncolytic virotherapy, as tumors develop structure and immune-evasion mechanisms in order to grow and ultimately spread. For these reasons, Onc.Ads modified to deliver structural or immune modulatory molecules (Armed Onc.Ads) have been developed to overcome the physical and immunological barriers of solid tumors. The combination of oncolysis with tumor microenvironment modulation/destruction may provide a promising platform for Ad-based cancer gene therapy.
| S-EPMC5138135 | biostudies-literature
Project description:Gastric cancer (GC) is an aggressive malignancy that is the third leading cause of cancer mortality worldwide. Localized GC can be cured with surgery, but most patients present with more advanced non-operable disease. Until recently, treatment options for relapsed and refractory advanced GC have been limited to combination chemotherapy regimens, HER-2 directed therapy, and radiation, which lead to few durable responses. Over the past decade, there have been significant advances in our understanding of the molecular and immune pathogenesis of GC. The infectious agents Epstein-Barr virus and Helicobacter pylori perturb the gastric mucosa immune equilibrium, which creates a microenvironment that favors GC tumorigenesis and evasion of immune surveillance. Insights into immune mechanisms of GC have translated into novel therapeutics, including immune checkpoint inhibitors, which have become a treatment option for select patients with GC. Furthermore, chimeric antigen receptor T-cell therapies have emerged as a breakthrough treatment for many cancers, with recent studies showing this to be a potential therapy for GC. In this review, we summarize the current state of knowledge on immune mechanisms of GC and the status of emerging immunotherapies to treat this aggressive cancer, as well as outline current challenges and directions for future research.
| S-EPMC8417143 | biostudies-literature
Project description:Central nervous system (CNS) metastases are common in patients with advanced non-small cell lung cancer (NSCLC), occurring in 24% to 44% of patients in the course of their disease and confer significant morbidity and mortality. Systemic therapies have been deemed ineffective in brain metastases (BM) under the hypothesis that the blood-brain barrier (BBB) limits their delivery to the brain. Angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF) pathway, is crucial for tumor survival, growth and invasion both in primary and metastatic brain lesions. Two major categories of agents have been developed to target this pathway: antibody-based agents and VEGF receptor tyrosine kinase inhibitors (TKIs). Clinical benefits have been shown with anti-angiogenetic therapies in the treatment of metastatic NSCLC. However, patients with CNS metastases were often excluded from trials with these agents, due to concerns about a potentially greater risk of cerebral haemorrhage and thromboembolic disease. Therefore, the overall efficacy and safety of angiogenetic agents in patients with BM from NSCLC are yet to be clarified. This paper aims to review available data about the efficacy and safety of anti-angiogenetic therapies for CNS metastases in NSCLC patients.
| S-EPMC5233881 | biostudies-other