Repurposing Drugs for Cancer Radiotherapy: Early Successes and Emerging Opportunities

It has long been recognized that combining radiotherapy with cytotoxic drugs such as cisplatin can improve efficacy. However, while concurrent chemoradiotherapy improves patient outcomes, it comes at costs of increased toxicity. A tremendous opportunity remains to investigate drug combinations in the clinical setting that might increase the benefits of radiation without additional toxicity. This chapter highlights opportunities to apply repurposing of drugs along with a mechanistic understanding of radiation effects on cancer and normal tissue to discover new therapy-modifying drugs and help rapidly translate them to the clinic. We survey candidate radiosensitizers that alter DNA repair, decrease hypoxia, block tumor survival signaling, modify tumor metabolism, block growth factor signaling, slow tumor invasiveness, impair angiogenesis, or stimulate antitumor immunity. Promising agents include widely used drugs such as aspirin, metformin, and statins, offering the potential to improve outcomes, decrease radiation doses, and lower costs. Many other candidate drugs are also discussed.
Source: The Cancer Journal - Category: Cancer & Oncology Tags: Review Articles Source Type: research

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We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we found that cofilin competes with tau for direct microtubule binding in vitro, in cells, and in vivo, which inhibits tau-induced microtubule assembly. Genetic reduction of cofilin mitigates tauopathy and synaptic defects in Tau-P301S mice and movement deficits in tau transgenic C. elegans. The pathogenic effects of cofilin are selectively mediated by activated cofilin, as active but not inactive cofilin selectively interacts with tubulin, destabilizes microtubules, and promotes tauopathy. These results therefore indicate that activated cofilin plays an essential intermediary role in neurotoxic signaling th...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study shows that mRNA levels of the aging related lamin A splice variant progerin, associated with premature aging in HGPS, were significantly upregulated in subjects with BMI ≥ 25 kg/m2. Moreover, our data revealed a significantly positive correlation of BMI with progerin mRNA. These data provide to our knowledge for the first-time evidence for a possible involvement of progerin in previously observed accelerated aging of overweight and obese individuals potentially limiting their longevity. Our results also showed that progerin mRNA was positively correlated with C-reactive protein (CRP). This might suggest an as...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Ryan R. Kelly1,2†, Lindsay T. McDonald1,2†, Nathaniel R. Jensen1,2, Sara J. Sidles1,2 and Amanda C. LaRue1,2* 1Research Services, Ralph H. Johnson VA Medical Center, Charleston, SC, United States 2Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States The significant biochemical and physiological effects of psychological stress are beginning to be recognized as exacerbating common diseases, including osteoporosis. This review discusses the current evidence for psychological stress-associated mental health disorders as risk factors for os...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract It has long been recognized that combining radiotherapy with cytotoxic drugs such as cisplatin can improve efficacy. However, while concurrent chemoradiotherapy improves patient outcomes, it comes at costs of increased toxicity. A tremendous opportunity remains to investigate drug combinations in the clinical setting that might increase the benefits of radiation without additional toxicity. This chapter highlights opportunities to apply repurposing of drugs along with a mechanistic understanding of radiation effects on cancer and normal tissue to discover new therapy-modifying drugs and help rapidly trans...
Source: Cancer Journal - Category: Cancer & Oncology Authors: Tags: Cancer J Source Type: research
When Tom Shicowich’s toe started feeling numb in 2010, he brushed it off as a temporary ache. At the time, he didn’t have health insurance, so he put off going to the doctor. The toe became infected, and he got so sick that he stayed in bed for two days with what he assumed was the flu. When he finally saw a doctor, the physician immediately sent Shicowich to the emergency room. Several days later, surgeons amputated his toe, and he ended up spending a month in the hospital to recover. Shicowich lost his toe because of complications of Type 2 diabetes as he struggled to keep his blood sugar under control. He wa...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized health Nutrition Source Type: news
In this study, scientists screened cells from old animals to identify any RBPs that change upon aging. The screening showed that one particular protein, Pumilio2 (PUM2), was highly induced in old animals. PUM2 binds mRNA molecules containing specific recognition sites. Upon its binding, PUM2 represses the translation of the target mRNAs into proteins. Using a systems genetics approach, the researchers then identified a new mRNA target that PUM2 binds. The mRNA encodes for a protein called Mitochondrial Fission Factor (MFF), and is a pivotal regulator of mitochondrial fission - a process by which mitochondria break u...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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