Advances in anti-BRAF therapies for lung cancer

SummaryNon-small cell lung cancer (NSCLC) is one of the most frequent causes of mortality in the western world. v-raf murine sarcoma viral oncogene homolog B (BRAF) is a member of the Raf kinase family and plays a critical role in cellular growth, proliferation, and differentiation through the mitogen-activated protein kinase pathway. The incidence of BRAF mutations in NSCLC is low, accounting for 0 –3% of all cases of lung cancer. Given the results obtained in metastatic melanoma, several studies have reported the efficacy of anti-BRAF therapies in NSCLC treatment. In this review, we describe changes in the landscape of BRAF-mutated lung cancer treatment and analyze insights from major clini cal trials in the context of future therapeutic prospects.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Conclusion: This case described here demonstrated that immunotherapy of PD-1 inhibitor is a promising treatment option for refractory MFS with PD-L1 positive or tumor mutational burden -high, which could contribute to effective tumor response.
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
We report five cases of BRAF V600E (substitution of glutamic acid for valine in codon 600) aberrant refractory metastatic cancers treated with dual BRAF/MEK combination inhibitor therapy leading to an excellent clinical and radiological response and protracted duration of disease control.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundNY-ESO-1 and LAGE-1a are antigens expressed in several tumours, including non-small cell lung cancer (NSCLC). Previous clinical trials using autologous T cells directed against NY-ESO-1/LAGE-1a have shown objective responses between 40% and 60% in synovial sarcoma, metastatic melanoma and multiple myeloma. Pembrolizumab (PEM) is a monoclonal antibody that blocks PD-1/PD-L1 interaction and increases anti-tumour activity in anti-tumour T cells. Here, PEM will be used in combination with NY-ESO-1/LAGE-1a T-cell receptor engineered patient T cells (GSK3377794) to potentially improve clinical benefit in this p...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Conclusions The recent, first randomized clinical trial demonstrated overall and progression free survival benefits after SBRT to oligometastatic disease which supports prior retrospective case series (6). The spine is a common site of metastatic bone disease, and as high quality data continue to mature, along with completion of additional randomized clinical trials, it is expected that utility of SBRT to the spine will increase in the future. Spine SBRT is unique due to the requirement of sharp dose falloff to prevent serious neurologic morbidity. With recent advances in radiotherapy planning, robotic patient positionin...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions and Future Perspectives It is now evident that NK/ILC family plays a pivotal role in the immune defenses. Recent studies in murine and human settings demonstrated that the expression of several inhibitory checkpoints, that may be detrimental in the tumor context, is not restricted to T lymphocytes, revealing an important, yet poorly appreciated, contribution of their expression on innate immune cells. Thus, in the recent years different immunotherapy approaches, based on the blockade of inhibitory NK cell receptors, have been developed in order to unleash NK cell cytotoxicity. This is particularly important in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions In the new era of targeted therapy, treatment options are increasingly based on the precise molecular and genetic profiling of tumor cells (58). Currently, the main challenge for further novel drug development in targeted therapy is the clarification of specific molecular mechanisms underlying the varied forms of tumors in clinic. It has been acknowledged that cancer is caused by a set of driver mutations. In this regard, it is of great significance to: (1) identify and validate key mutant genes and proteins in cancers as new targets; (2) identify patients most likely and unlikely to benefit from certain targe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
la Silvestris Despite that the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitourinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response such as PD-L1 expression, tumor...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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