A Computer - Aided Drug Designing for Pharmacological inhibition of ALK inhibitors induces apoptosis and differentiation in Non-small cell lung cancer.

CONCLUSION: These investigations denotes that virtual screened compound (PubChem CID- 123449015) is more efficient to be a better prospective candidate for NSCLC treatment having good pharmacological profile than the pre-established compound CEP-37440 (PubChem CID- 71721648) with low rerank score. The identified virtual screened drug have a high potential to act as ALK inhibitors and can show promising results in the research of non-small cell lung cancer (NSCLC). PMID: 31109278 [PubMed - as supplied by publisher]
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research

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Abstract Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, is a therapeutic target in various cancers, including non-small cell lung cancer. Although several ALK inhibitors, including crizotinib, ceritinib, and alectinib, are approved for cancer treatment, their long-term benefit is often limited by the cancer's acquisition of resistance owing to secondary point mutations in ALK. Importantly, some ALK inhibitors cannot cross the blood-brain barrier (BBB) and thus have little or no efficacy against brain metastases. The introduction of a lipophilic moiety, such as a fluoroethyl group may impr...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
Authors: Hamilton G, Hochmair MJ Abstract Introduction: Brigatinib is a second-line inhibitor for the treatment of rearranged anaplastic lymphoma kinase (ALK) in lung cancer patients which has significant activity against brain metastases. This tyrosine kinase inhibitor (TKI) overcomes a wide range of ALK mutations which confer therapeutic resistance and is increasingly applied in first-line therapy due to improved benefit for patients compared to crizotinib, the current standard of care. Areas covered: The authors review the development and characteristics of brigatinib and discuss the optimal clinical use and seq...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
Abstract Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (3 to 5% of all non-small cell lung cancers) carries a particularly high risk of central nervous system dissemination (60% to 90%). As the use of ALK inhibitors improves treatment outcomes over chemotherapy, the determent of central nervous system metastases has become an increasingly relevant therapeutic dilemma considering young age and possible extended overall survival. The goal of brain metastases management is to optimize both overall survival and quality of life, with the high priority of neurocognitive function preservation. Unfo...
Source: Cancer Radiotherapie - Category: Cancer & Oncology Authors: Tags: Cancer Radiother Source Type: research
We assessed four anaplastic lymphoma kinase (ALK) ‐positive non‐small cell lung cancer (NSCLC) patients who were treated with ALK‐tyrosine kinase inhibitors (TKIs). They developed brain radiation necrosis and brain oedema after stereotactic irradiation. Here, we report the efficacy and safety of bevacizumab given in combination with ALK‐TKI s for brain radiation necrosis in ALK‐positive NSCLC. Central nervous system (CNS) metastases from anaplastic lymphoma kinase (ALK) ‐positive lung cancer often results in failure of ALK‐tyrosine kinase inhibitor (TKI) therapy. Patients with uncontrolled CNS metastases rece...
Source: Respirology Case Reports - Category: Respiratory Medicine Authors: Tags: Case Series Source Type: research
BackgroundTyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non ‐small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) ‐mutation or anaplastic lymphoma kinase (ALK) ‐rearrangement. However, the real‐world evaluation status of ALK/EGFR in China remains unclear.MethodsWe conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb –IV) at 12 Chinese hospitals.ResultsThe most common evaluation methods were amplification ‐refractory mutation system forEGFR status an...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Conclusion: These novel fluoroethyl ALK inhibitor analogues show promise for enhanced blood brain barrier penetration and therapeutic potential in the central nervous system (CNS).
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Preclinical Probes for Oncology Posters Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology 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
ConclusionIn cases of anaplastic lymphoma kinase-positive lung cancer poorly responsive to anaplastic lymphoma kinase inhibitors, re-examination of the tissue should be considered because there is a possibility of anaplastic lymphoma kinase-positive adenosquamous carcinoma.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
ConclusionsALK-rearranged advanced NSCLC patients with baseline brain metastasis can still achieve OS benefits from crizotinib treatment. However, patients with intracranial progression may not obtain a  long-term survival benefit from continuation of CBPD.
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
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