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Mashup Score: 15Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer - 18 day(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.
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 4
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: 30TREX1 Inactivation Unleashes Cancer Cell STING–Interferon Signaling and Promotes Antitumor Immunity - 19 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: 8To Conquer KRAS, Drugmakers Take Aim at More Mutations - 19 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.
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Mashup Score: 11Glioma Approval Sets New Course in Pediatric Drug Development - 19 day(s) ago
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.
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Mashup Score: 3Why Kidney Cancer Rates Differ Globally - 19 day(s) ago
An international genomics study has revealed distinct mutational signatures in kidney cancer that vary across different regions, illuminating the reasons behind global disparities in incidence rates. Highlighting the effect of both recognized and unidentified mutation-inducing agents, the research underscores the need for targeted public health interventions and further studies into the environmental factors linked to renal cell carcinoma.
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Mashup Score: 3
Major Finding: Atypical memory (AtM) B cells reside within the tumor microenvironment and suppress antitumor immunity. Concept: A single-cell, B-cell atlas reveals a noncanonical pathway of B-cell maturation that impacts prognosis. Impact: This study highlights mechanisms that inform the development of B-cell–targeted immunotherapies.
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Mashup Score: 3IGSF8 on Cancer Cells Suppresses NK Cell–Mediated Cytotoxicity - 20 day(s) ago
Major Finding: IGSF8 is highly expressed on cancer cells and inhibits human NK cell function by binding to KIR3LD2. Concept: An antibody developed to block the IGSF8−KIR3LD2 interaction shows antitumor effects alone or with anti-PD1. Impact: These results suggest that IGSF8 could be exploited as a potential immunotherapeutic target in cancer.
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Mashup Score: 17Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms - 20 day(s) ago
A dual-recombinase reversible knock-in/knock-out mouse model of Jak2V617F validates the absolute requirement of Jak2V617F in sustaining myeloproliferative neoplasms and provides rationale for the clinical development of mutant-selective JAK2V617F inhibitors.
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Mashup Score: 126CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma - 20 day(s) ago
AbstractTherapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC a
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
New from the May issue— Sequential chemoimmunotherapy in #gastriccancer, by @AnMinae, @arnavmehta3, Byung Hoon Min, You Jeong Heo, Seung Tae Kim, @KlempnerSam, @JeeyunM et al. https://t.co/cpLioC6wpp @MGHCancerCenter @Broadinstitute #SamsungMedicalCenter @SU2Cscience https://t.co/JvoP5os1wD