Brain metastases in ALK-positive NSCLC - time to adjust current treatment algorithms.

Brain metastases in ALK-positive NSCLC - time to adjust current treatment algorithms. Oncotarget. 2018 Oct 12;9(80):35181-35194 Authors: Griesinger F, Roeper J, Pöttgen C, Willborn KC, Eberhardt WEE Abstract The progress in molecular biology has revolutionized systemic treatment of advanced non-small-cell lung cancer (NSCLC) from conventional chemotherapy to a treatment stratified by histology and genetic aberrations. Tumors harboring a translocation of the anaplastic-lymphoma-kinase (ALK) gene constitute a distinct genetic and clinico-pathologic NSCLC subtype with patients with ALK-positive disease being at a higher risk for developing brain metastases. Due to the introduction of effective targeted therapy with ALK-inhibitors, today, patients with advanced ALK-positive NSCLC achieve high overall response rates and remain progression-free for long time intervals. Moreover, ALK-inhibitors seem to exhibit efficacy in the treatment of brain metastases. In the light of this, it needs to be discussed how treatment algorithms for managing patients with brain metastases should be modified. By integrating systemic ALK-inhibitor therapy, radiotherapy, in particular whole brain radiotherapy might be postponed deferring potential long-term impairment by neurocognitive deficits to a later time point in the course of the disease. An early treatment of asymptomatic brain metastases might offer patients a longer time without impairment of cerebral symptoms or radio...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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Authors: Pfeifer CR, Irianto J, Discher DE Abstract As a cancer cell invades adjacent tissue, penetrates a basement membrane barrier, or squeezes into a blood capillary, its nucleus can be greatly constricted. Here, we examine: (1) the passive and active deformation of the nucleus during 3D migration; (2) the nuclear structures-namely, the lamina and chromatin-that govern nuclear deformability; (3) the effect of large nuclear deformation on DNA and nuclear factors; and (4) the downstream consequences of mechanically stressing the nucleus. We focus especially on recent studies showing that constricted migration caus...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Schumacher L Abstract Collective cell migration is a key process in developmental biology, facilitating the bulk movement of cells in the morphogenesis of animal tissues. Predictive understanding in this field remains challenging due to the complexity of many interacting cells, their signalling, and microenvironmental factors - all of which can give rise to non-intuitive emergent behaviours. In this chapter we discuss biological examples of collective cell migration from a range of model systems, developmental stages, and spatial scales: border cell migration and haemocyte dispersal in Drosophila, gastrula...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Banerjee S, Marchetti MC Abstract Collective cell migration plays a central role in tissue development, morphogenesis, wound repair and cancer progression. With the growing realization that physical forces mediate cell motility in development and physiology, a key biological question is how cells integrate molecular activities for force generation on multicellular scales. In this review we discuss recent advances in modeling collective cell migration using quantitative tools and approaches rooted in soft matter physics. We focus on theoretical models of cell aggregates as continuous active media, where the...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Yang Y, Jolly MK, Levine H Abstract Collective cell migration plays key roles in various physiological and pathological processes in multicellular organisms, including embryonic development, wound healing, and formation of cancer metastases. Such collective migration involves complex crosstalk among cells and their environment at both biochemical and mechanical levels. Here, we review various computational modeling strategies that have been helpful in decoding the dynamics of collective cell migration. Most of such attempts have focused either aspect - mechanical or biochemical regulation of collective cel...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
CONCLUSION: In this review, the recent findings about the renoprotective agents were evaluated and screened with respect to the use of 99mTc-DMSA , which is preclinically and clinically used for animal cases and cancer patients under the treatment by radiotherapy and chemotherapy. PMID: 31612808 [PubMed - in process]
Source: Current Radiopharmaceuticals - Category: Radiology Tags: Curr Radiopharm Source Type: research
Conclusion: These observations disclosed that Ras-ERK1/2 promoted the development of lung cancer via decreasing H3K18ac through MDM2-mediated GCN5 degradation. These findings might provide a new therapeutic strategy for lung cancer. PMID: 31613681 [PubMed - in process]
Source: Pharmaceutical Biology - Category: Drugs & Pharmacology Tags: Pharm Biol Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology 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
Lung cancer is the most common tumor and the leading cause of cancer-related death worldwide. Approximately 6.7% of non-small-cell lung cancers (NSCLCs) show anaplastic lymphoma kinase (ALK) rearrangement and could benefit from ALK-targeted treatment. Various anti-ALK drugs have been developed during the past years, but it is actually controversial which sequence and which ALK inhibitor is recommended for a single patient. Leptomeningeal carcinomatosis (LC) is associated with a poor prognosis, with an overall survival of 2–4 months for treated patients. The data about LC management derive mainly from retrospective st...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: CASE REPORTS Source Type: research
Conclusions:Early recognition of new neurological patterns of toxicity may lead to drug discontinuation or dose adjustment preventing further neurological deterioration. A better knowledge of these toxicities will help differentiate treatment-related complications from metastatic progression.
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: P14 Neurotoxicity and neuroprotection Source Type: research
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