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Mashup Score: 0Adverse Metaphase Cytogenetics Can Be Overcome by Adding Bortezomib and Thalidomide to Fractionated Melphalan Transplants - 2 hour(s) ago
Abstract. Purpose: To determine whether a reduction in the intensity of Total Therapy (TT) reduces toxicity and maintains efficacy.Experimental Design: A total of 289 patients with gene expression profiling (GEP70)-defined low-risk multiple myeloma were randomized between a standard arm (TT4-S) and a light arm (TT4-L). TT4-L employed one instead of two inductions and consolidations. To compensate for potential loss of efficacy of TT4-L, bortezomib and thalidomide were added to fractionated melphalan 50 mg/m2/d for 4 days.Results: Grade ≥3 toxicities and treatment-related mortalities were not reduced in TT4-L. Complete response (CR) rates were virtually identical (P = 0.2; TT4-S, 59%; TT4-L, 61% at 2 years), although CR duration was superior with TT4-S (P = 0.05; TT4-S, 87%; TT4-L, 81% at 2 years). With a median follow-up of 4.5 years, there was no difference in overall survival (OS) and progression-free survival (PFS). Whereas metaphase cytogenetic abnormalities (CAs) tended to be an a
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 0Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer - 7 hour(s) ago
A phase II sequential chemoimmunotherapy trial in frontline stomach cancer demonstrates the importance of early tumor microenvironment remodeling to inform patients who benefit from adding the anti–PD-1 inhibitor pembrolizumab.
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Mashup Score: 1
AbstractAlterations in the RAS–MAPK signaling cascade are common across multiple solid tumor types and are a driver for many cancers. NST-628 is a potent pan-RAF–MEK molecular glue that prevents the phosphorylation and activation of MEK by RAF, overcoming the limitations of traditional RAS–MAPK inhibitors and leading to deep durable inhibition of the pathway. Cellular, biochemical, and structural analyses of RAF–MEK complexes show that NST-628 engages all isoforms of RAF and prevents the formation of BRAF–CRAF heterodimers, a differentiated mechanism from all current RAF inhibitors. With a potent and durable inhibition of the RAF–MEK signaling complex as well as high intrinsic permeability into the brain, NST-628 demonstrates broad efficacy in cellular and patient-derived tumor models harboring diverse MAPK pathway alterations, including orthotopic intracranial models. Given its functional and pharmacokinetic mechanisms that are differentiated from previous therapies, NST-628 is positi
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 0
AbstractBackground:. Digital mammography has replaced film mammography in breast-screening programs globally, including Australia. This led to an increase in the rate of detection, but whether there was increased detection of clinically important cancers is uncertain.Methods:. In this population-wide retrospective cohort study in New South Wales, Australia spanning 2004 to 2016 and including 4,631,656 screens, there were 22,965 cancers in women screened with film (n = 11,040) or digital mammography (n = 11,925). We examined the change in tumor characteristics overall and how these rates changed over time, accounting for changes in background rates using an interrupted time-series. Comparisons were made with unscreened women (n = 26,326) during this time.Results:. We found increased detection of in situ cancer (3.36 per 10,000 screens), localized invasive, and smaller-sized breast cancers attributable to the change in mammography technology, whereas screen-detected intermediate-sized an
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Mashup Score: 0
The repositioning of shelved assets for pediatric applications presents a promising avenue for advancing therapies for childhood tumors. Tovorafenib, originally intended for adult melanoma, received approval in April as a treatment for pediatric low-grade glioma. This success has spurred hopes within the industry of replicating this achievement with other previously discontinued drug candidates.
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 22TREX1 Inactivation Unleashes Cancer Cell STING–Interferon Signaling and Promotes Antitumor Immunity - 1 day(s) ago
Preventing the feedback induction of TREX1 downstream of tumor cell STING results in robust interferon signaling and can render cancer cells vulnerable to NK and other immune cell–mediated killing, as well as immune checkpoint blockade.
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 4To Conquer KRAS, Drugmakers Take Aim at More Mutations - 1 day(s) ago
Drugmakers are expanding their attack on KRAS mutations, with clinical trials now underway for therapies targeting the common G12D variant, as well as broader pan-RAS inhibitors. As reported at the American Association for Cancer Research Annual Meeting 2024, the multi-selective drug strategy is showing early promise, offering hope for more effective treatments across a wide range of RAS-driven cancers.
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 2
Abstract. Many cancer patients are at risk of developing cognitive symptoms that often become evident during or after cancer-directed therapy and may involve difficulties with attention, concentration, multitasking, executive function, and memory. Despite recent advances in identifying potential molecular and cellular mechanisms underlying cancer and chemotherapy-related cognitive impairment, there is generally a lack of effective treatment strategies, and the development of novel therapeutic interventions represents a major unmet medical need in clinical practice. A recent study by Kim and colleagues suggests that multi-sensory 40-Hz gamma entrainment using sensory stimuli (GENUS) with combined visual and auditory stimuli is associated with powerful neuroprotective effects in mouse models of cisplatin or methotrexate-induced ‘chemobrain’. While the study has some limitations and successful interventions in animal models have often failed to translate into clinical practice, this non-i
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Mashup Score: 10
The repositioning of shelved assets for pediatric applications presents a promising avenue for advancing therapies for childhood tumors. Tovorafenib, originally intended for adult melanoma, received approval in April as a treatment for pediatric low-grade glioma. This success has spurred hopes within the industry of replicating this achievement with other previously discontinued drug candidates.
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 20
Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1.
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet-
New in Convergence Science from the May 1 issue— Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with EMT & Inflammation in Cancer Cells in PDAC, by Samantha Guinn, @DrRABurkhart, @FertigLab, @JZimmermanMDPhD et al. https://t.co/3RATluwLuh @ConvergenceInst https://t.co/TLHPNiaHGX
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We will be publishing soon data on TT IV focusing only on patients with standard risk myeloma All those approaches didn’t use upfront Dara (anti-CD38) therapy and intended to do tandem auto transplant Earlier results published a while ago: https://t.co/c7AN0kns5l