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6 days ago | 
nature.com | David Killock
The covalent KRAS-G12C inhibitors adagrasib and sotorasib are approved for patients with previously treated KRASG12C-mutant non-small-cell lung cancer (NSCLC) or colorectal cancer (CRC); however, the efficacy of these agents is limited, in large part, by suboptimal target engagement.
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3 weeks ago | 
nature.com | David Killock
Patients with progression of metastatic triple-negative breast cancer (mTNBC) following first-line treatment have a dismal prognosis. The TROP2-directed antibody–drug conjugate (ADC) sacituzumab govitecan improves outcomes in this setting. New data from the phase III OptiTROP-Breast01 trial support sacituzumab tirumotecan (sac-TMT), a different anti-TROP2 ADC with a linker designed for improved bioactivity, as another treatment option for such patients.
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2 months ago | 
nature.com | David Killock
Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Most patients have considerable tumour shrinkage after IC, yet the radiotherapy target volume is calculated on the basis of the dimensions of the pretreatment tumour, which can result in debilitating toxicities owing to irradiation of surrounding functional structures.
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Jan 31, 2025 | 
nature.com | David Killock
Two multimodal treatment strategies, perioperative chemotherapy and preoperative chemoradiotherapy, have been shown to improve overall survival (OS) compared to surgery alone in patients with locally advanced oesophageal adenocarcinoma (EAC); however, the optimal approach has been unclear. Newly published results from the phase III ESOPEC trial demonstrate the superiority of the perioperative strategy.
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Jan 20, 2025 | 
nature.com | David Killock
Haematopoietic stem cell transplantation (HSCT) and CD19-targeted chimeric antigen receptor (CAR) T cells are potentially curative therapies for relapsed and/or refractory diffuse large B cell lymphoma (R/R DLBCL); however, many patients are unable to receive or have further relapse following these treatments.
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Jan 1, 2025 | 
nature.com | David Killock
Various endocrine therapies and CDK4/6 inhibitors have improved the treatment of ER+HER2−breast cancer, although resistance remains common and often involves ESR1 (encoding ERα) mutations. Now, data from the phase III EMBER-3 trial demonstrate that the next-generation, brain-penetrant, oral selective ER degrader imlunestrant delays disease progression in previously treated patients with ESR1 mutations, and regardless of ESR1 status when combined with abemaciclib.
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Jan 1, 2025 | 
nature.com | David Killock
Sequencing of plasma cell-free DNA (cfDNA) is commonly performed during pregnancy to screen for fetal aneuploidy. Now, data from the ongoing prospective IDENTIFY study demonstrate that this strategy also enables prompt detection of occult maternal cancers.
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Dec 20, 2024 | 
science.org | Justin Joachim |Davide Maselli |Jurjan Aman |Pamela Swiatlowska |David Killock |Hiba Chaudhry | +10 more
MATERIALS AND METHODS Anti–p-ERM/anti–p-Dmoesin (Cell Signaling Technology, 3141), anti-GST (ChromoTek, 6G9), anti–p-Thr (Cell Signaling Technology, 9381), anti-GFP for Western blotting (ChromoTek, 3H9), anti-GFP for immunofluorescence detection of YFP-TNIK (Roche, 11814460001), anti-TNIK (Santa Cruz Biotechnology, sc-136103), anti-Actin (Sigma-Aldrich, A2228), anti–p-MLC2 Ser19 (Cell Signaling Technology, 3671), anti-Ezrin (Cell Signaling Technology, 3145), anti-moesin (Cell Signaling...
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Nov 26, 2024 | 
nature.com | David Killock
Many patients with advanced-stage gastric or gastro-oesophageal junction cancer (G/GEJC), particularly those deemed ineligible for combination therapy incorporating antibodies targeting HER2, PD-1 or claudin-18.2, receive chemotherapy alone in the first line. Disease progression typically occurs within a few months and the associated morbidities often preclude standard second-line treatment with ramucirumab plus paclitaxel.
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Nov 12, 2024 | 
nature.com | David Killock
Approximately 40% of hormone receptor-positive (HR+), HER2-negative (HER2–) breast cancers harbour activating mutations in PIK3CA (encoding the catalytic subunit of PI3Kα); these mutations are generally associated with a poor prognosis but also responsiveness to inhibitors of the PI3K–AKT pathway.
