Cancer Discovery

Journal Information
ISSN / EISSN : 2159-8274 / 2159-8290
Total articles ≅ 5,551
Current Coverage
SCOPUS
LOCKSS
MEDICUS
MEDLINE
PUBMED
SCIE
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SHERPA/ROMEO
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Latest articles in this journal

Abstract:
A computational model of resilient T cells predicts immunotherapy response via transcriptomic data.
Abstract:
Somatic mutations in CCL22 were found in a distinct subset of CLPD-NK and drive disease development.
Abstract:
Intermittent dosing of PI3Kδ inhibitors (PI3Kδi) reduces tumor growth and immune-related adverse events.
Andreas Weiss, Edwige Lorthiois, Louise Barys, Kim S. Beyer, Claudio Bomio-Confaglia, Heather Burks, Xueying Chen, XiaoMing Cui, , Lekshmi Dharmarajan, et al.
Abstract:
Covalent inhibitors of KRASG12C have shown antitumor activity against advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor of GDP-bound KRASG12C that forms novel interactions with the switch II pocket. JDQ443 potently inhibits KRASG12C-driven cellular signaling and demonstrates selective antiproliferative activity in KRASG12C-mutated cell lines, including those with G12C/H95 double mutations. In vivo, JDQ443 induces AUC exposure-driven antitumor efficacy in KRASG12C-mutated cell-derived (CDX) and patient-derived (PDX) tumor xenografts. In PDX models, single-agent JDQ443 activity is enhanced by combination with inhibitors of SHP2, MEK, or CDK4/6. Notably, the benefit of JDQ443 plus the SHP2 inhibitor TNO155 is maintained at reduced doses of either agent in CDX models, consistent with mechanistic synergy. JDQ443 is in clinical development as monotherapy and in combination with TNO155, with both strategies showing antitumor activity in patients with KRASG12C-mutated tumors. Significance: JDQ443 is a structurally novel covalent KRASG12C inhibitor with a unique binding mode that demonstrates potent and selective antitumor activity in cell lines and in vivo models. In preclinical models and patients with KRASG12C-mutated malignancies, JDQ443 shows potent antitumor activity as monotherapy and in combination with the SHP2 inhibitor TNO155.
Abstract:
Metallo-β-lactamase domain-containing protein 2 (MBLAC2) is a major off-target of histone deacetylase (HDAC) inhibitors.
Abstract:
The FDA has proposed a ban on menthol flavoring in cigarettes. If enacted, the prohibition would increase smoking cessation rates and decrease first-time tobacco use, in turn drastically reducing smoking-related cancer deaths.
Abstract:
The ketone body β-hydroxybutyrate (BHB) mediates the growth inhibitory effects of the ketogenic diet (KD).
Abstract:
The engineered IL2 cytokine bempegaldesleukin fell flat in multiple late-stage clinical studies, prompting its developers—Nektar Therapeutics and Bristol Myers Squibb—to halt its clinical development. However, a pipeline of diverse IL2-based therapies may yet succeed.
Zachary Jackson, Changjin Hong, Robert Schauner, , Paolo F. Caimi, , Maria Florencia. Giraudo, Kalpana Gupta, Jane S. Reese, , et al.
Abstract:
Chimeric antigen receptor T cell (CAR-T) therapy directed at CD19 produces durable remissions in the treatment of relapsed/refractory non-Hodgkin's lymphoma (NHL). Nonetheless, many patients receiving CD19 CAR-T cells fail to respond for unknown reasons. To reveal changes in 4-1BB-based CD19 CAR-T cells and identify biomarkers of response, we employed single cell RNA sequencing and protein surface marker profiling of patient CAR-T cells pre- and post-infusion into NHL patients. At the transcriptional and protein levels, we note the evolution of CAR-T cells toward a non-proliferative, highly differentiated, and exhausted state, with an enriched exhaustion profile in CAR-T cells of patients with poor response marked by TIGIT expression. Utilizing in vitro and in vivo studies, we demonstrate TIGIT blockade alone improves the anti-tumor function of CAR-T cells. Altogether, we provide evidence of CAR-T cell dysfunction marked by TIGIT expression driving a poor response in NHL patients.
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