New drug target can break down cancer's barrier against treatment

Targeting a molecule in blood vessels can make cancer therapy significantly more effective, according to research. Researchers have found that a molecule, called focal adhesion kinase (FAK), signals the body to repair itself after chemotherapy or radiotherapy, which kill cancer cells by damaging DNA. When the researchers removed FAK from blood vessels that grew in melanoma or lung cancer models, both chemotherapy and radiation therapies were far more effective in killing the tumors.
Source: ScienceDaily Headlines - Category: Science Source Type: news

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DNA-damaging chemotherapy and radiation therapy are integrated into the treatment paradigm of the majority of cancer patients. Recently, immunotherapy that targets the immunosuppressive interaction between programmed death 1 (PD-1) and its ligand PD-L1 has been approved for malignancies including non–small cell lung cancer, melanoma, and head and neck squamous cell carcinoma. ATR is a DNA damage–signaling kinase activated at damaged replication forks, and ATR kinase inhibitors potentiate the cytotoxicity of DNA-damaging chemotherapies. We show here that the ATR kinase inhibitor AZD6738 combines with conformal r...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Publication date: Available online 10 August 2018Source: Journal of Geriatric OncologyAuthor(s): Joobin Sattar, Adi Kartolo, Wilma M. Hopman, Joshua Matthew Lakoff, Tara BaetzAbstractImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and Participants...
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
Purpose of review The advent of immunotherapy significantly improved clinical outcomes in cancer patients, although immune checkpoint blockade (ICB) still lack of efficacy in a consistent proportion of treated patients. The purpose of this article is to review the most innovative and clinically promising ICB-based combinations designed to improve the efficacy of cancer immunotherapy. Recent findings First-line combinatorial treatment with ipilimumab and nivolumab has recently shown to be superior to the standard of care in a subset of metastatic nonsmall cell lung cancer (NSCLC) and renal cell carcinoma (RCC). The com...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research
AbstractDabrafenib is a potent and selective inhibitor of BRAF-mutant kinase that is approved, as monotherapy or in combination with trametinib (mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor), for unresectable or metastaticBRAF-mutated melanoma, advanced non-small cell lung cancer and anaplastic thyroid cancer harbouring theBRAFV600E mutation. The recommended dose of dabrafenib is 150  mg twice daily (bid) under fasted conditions. After single oral administration of the recommended dose, the absolute oral bioavailability (F) of dabrafenib is 95%. Dabrafenib shows a time-dependent increase in appa...
Source: Clinical Pharmacokinetics - Category: Drugs & Pharmacology Source Type: research
Introduction: Binding of programmed cell death 1 (PD-1) ligands to PD-1 receptors found on T cells, inhibits T-cell proliferation and contributes to immune tolerance and inhibition of tumor surveillance. Nivolumab is a monoclonal antibody that binds to PD-1 receptor and inhibits this pathway. Given its antitumor capabilities, this medication was recently approved in Canada and the U.S. for the treatment of unresectable or metastatic melanoma, metastatic nonsmall cell lung cancer, renal carcinoma, and classical Hodgkin lymphoma.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
Background: The FAMMM syndrome with the CDKN2A mutation is a major hereditary cause of malignant melanoma. In addition to melanoma, there is a high incidence of pancreatic cancer, breast cancer, and lung cancer in CDKN2A families. We were interested in determining the incidence of other malignancies not known to be associated (discordant) with FAMMM syndrome.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
We examined the accepted biomarker of vitamin D status, serum 25-hydroxyvitamin D [25(OH)D], and cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Of 4616 cancer cases with measured serum 25(OH)D, 2884 died of their cancer during 28  years of follow-up and 1732 survived or died of other causes. Proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between pre-diagnostic 25(OH)D and overall and site-specific survival. Serum 25(OH)D was significantly lower among cases who subsequently died from their malignancy compared with those...
Source: European Journal of Epidemiology - Category: Epidemiology Source Type: research
Heating metals to very high temperatures can be incredibly dangerous for the 111 million people around the world who weld. The culprits are welding fumes, as well as exposure to radiation and asbestos, according to scientists at the International Agency for Research on Cancer. These toxins can potentially cause lung cancer, kidney cancer, and melanoma of the eye, as well as other health problems.08/01/2018
Source: Kidney Cancer Association - Category: Urology & Nephrology Source Type: news
In this study we selected 58 consecutive NSCLC surgical specimens that underwent pathologic examination from January 2014 to July 2015. Using a tissue microarray approach we evaluated the IHC expression of PD-L1 in tumor-infiltrating lymphocytes and tumor cells (TCs) and compared the ICH staining with tumor histology, grade and the age of the tissue blocks. The main new finding was the fading of PD-L1 IHC expression in TCs in tissues processed in 2014 compared with 2015. PD-L1 expression in tumor-infiltrating lymphocytes in the 2 years was similar. We also found a significant higher immunoreactivity of TCs in high grade NS...
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Research Articles Source Type: research
Cardiac tumors have generally been considered to be rare. They are often found incidentally as they tend to remain clinically silent, but they can sometimes present with symptoms secondary to obstruction, embolization, or invasion of the myocardium. Most cardiac tumors are secondary tumors from metastases, with primary cardiac tumors constituting approximately 15% of all cardiac tumors1. Although melanoma and pleural mesothelioma often have cardiac involvement, the most common cancers to be identified in cardiac metastases are lung cancer (36-39%), breast cancer (10-12%), and hematologic cancers (10-21%)2.
Source: The American Journal of Medicine - Category: General Medicine Authors: Tags: Clinical Communication to the Editor Source Type: research
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