Melissa L. Johnson
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View article: Two Phase II Trials of Adavosertib, a Wee1 Inhibitor with Docetaxel or Carboplatin plus Pemetrexed in Non-small-cell Lung Cancer
Two Phase II Trials of Adavosertib, a Wee1 Inhibitor with Docetaxel or Carboplatin plus Pemetrexed in Non-small-cell Lung Cancer Open
ClinicalTrials.gov, NCT02087241 and NCT02087176.
View article: Ifinatamab Deruxtecan in Patients With Extensive-Stage Small Cell Lung Cancer: Primary Analysis of the Phase II IDeate-Lung01 Trial
Ifinatamab Deruxtecan in Patients With Extensive-Stage Small Cell Lung Cancer: Primary Analysis of the Phase II IDeate-Lung01 Trial Open
PURPOSE Treatment options for patients with recurrent or progressive extensive-stage small cell lung cancer (ES-SCLC) are limited. This phase II trial evaluated the efficacy and safety of ifinatamab deruxtecan (I-DXd), a B7 homolog 3–direc…
View article: The Phase 2b COPERNICUS Study of Subcutaneous Amivantamab with Lazertinib as First-Line Treatment, or with Chemotherapy as Second-Line Treatment, for EGFR-Mutated Non-Small Cell Lung Cancer: a Vodcast
The Phase 2b COPERNICUS Study of Subcutaneous Amivantamab with Lazertinib as First-Line Treatment, or with Chemotherapy as Second-Line Treatment, for EGFR-Mutated Non-Small Cell Lung Cancer: a Vodcast Open
COPERNICUS uses a pragmatic study design to evaluate the efficacy and safety of subcutaneous amivantamab regimens combined with advancements in supportive care to prevent and proactively manage AEs in a diverse participant population. Supp…
View article: A prospective outcomes and cost-effective analysis of surgery compared to stereotactic body radiation therapy for stage I non-small cell lung cancer
A prospective outcomes and cost-effective analysis of surgery compared to stereotactic body radiation therapy for stage I non-small cell lung cancer Open
Central Institutional Review Board (IRB) approval was obtained under expedited review and deemed minimal risk to patients (WCG Clinical IRB00000533 Study 1171593). All participating sites obtained local IRB approval before study initiation…
View article: Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non–Small Cell Lung Cancer After Platinum-Based Chemotherapy and Immunotherapy
Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non–Small Cell Lung Cancer After Platinum-Based Chemotherapy and Immunotherapy Open
PURPOSE Patritumab deruxtecan (HER3-DXd; MK-1022) is an investigational HER3-directed antibody-drug conjugate composed of a human immunoglobulin G1 monoclonal antibody to HER3 (patritumab) covalently linked via a stable tetrapeptide-based …
View article: Supplementary Tables S1-S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary Tables S1-S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Supplementary Table S1. Sensitivity of Various Cell Lines to Reactivator Compound PC14586. Supplementary Table S2. Cell Line Information for Cells Used in the Paper. Supplementary Table S3. Antibodies Used to Detect Specific Antigens in Tu…
View article: Figure 5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Pharmacologic activation of WT p53 inhibited tumor growth and induced immunologic cell changes in tumors. A, Average tumor volume (mm3; left), AUC analysis of tumor growth (middle), and percentage of body weight change (r…
View article: Supplementary Figures S1-S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary Figures S1-S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Supplementary Figure S1. Functional Characterization of p53-Y220C Reactivator Compounds. Supplementary Figure S2. Reactivator Compounds are Active Only in p53-Y220C Cell Lines. Supplementary Figure S3. Selective Restoration of Wild-Type (W…
View article: Figure 1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Functional characterization of p53-Y220C reactivator compounds and restoration of WT p53 function in cells. A, Structure of p53 reactivators and biochemical properties. The concentration of the test compound required to increase Y22…
View article: Supplementary File S6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in T3M-4 cells treated by PC14586 (5 µM) vs. DMSO control (16 h).
View article: Supplementary File S12 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S12 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
The restoration of the p53 signaling pathway in vivo was assessed via p53 pathway profiling analysis in NUGC-3 xenografted tumors after 6 days of 100-mg/kg PC14586 administration.
View article: Supplementary File S16 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S16 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
GSEA analysis using MSigDB Hallmark gene sets collection (H) for all detected genes demonstrated the regulation of genes for immune and inflammatory response in vivo in NUGC-3 xenograft tumors following 8 h of treatment with 100 mg/kg PC14…
View article: Figure 2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Selective restoration of WT p53 transcriptional responses by PC14586 in cells. A, Quantification of CDKN1A (p21) and MDM2 mRNA by qRT-PCR in p53-Y220C, other p53 hotspot mutants, p53 WT, and p53 KO cell lysates followi…
View article: Figure 4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
PC14586 restored multiple facets of dynamic WT p53 transcriptional responses in vivo. A, Time-dependent effects of PC14586 on gene expression of key p53 targets, CDKN1A, MDM2, and BIRC5, with repeat daily…
View article: Supplementary File S15 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S15 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
The immune pathway changes with PC14374 administration in vivo based on the Nanostring data from Hupki-MT373 tumors treated with vehicle versus PC14374 at 150 or 300 mg/kg for 2Q7D×2 or 2Q7D×3.
View article: Supplementary File S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S10 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S10 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Annotated gene differential expression (DE) analysis from RNA-seq data in 4 cell lines (NUGC-3, T3M-4, NUGC-3 KO, and SJSA-1) treated with rezatapopt (PC14586, 5 µM) versus DMSO (5 and 16 h).
View article: Supplementary File S13 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S13 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Annotated analysis of differential gene expression (DE) from RNA-seq data in NUGC-3 xenografted tumors over 6 days of 100 mg/kg PC14586 administration.
View article: Supplementary File S14 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S14 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
GSEA analysis of DEGs shows the restoration of WT p53 transcriptional responses by PC14586 in vivo in NUGC-3 xenografted tumors over 6 days of 100-mg/kg PC14586.
View article: Supplementary File S3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 KO cells treated by PC14586 (5 µM) vs. DMSO control (16 h).
View article: Figure 3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Pharmacologic activation of WT p53 in p53-Y220C xenografts induced p53 signaling and inhibited tumor growth. A and B, PC14586 was administered orally at the indicated doses to p53-Y220C–expressing (A) NUGC-3 and (B<…
View article: Supplementary File S9 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S9 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in SJSA-1 cells treated by PC14586 (5 µM) vs. DMSO control (16 h).
View article: Data from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Data from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series …
View article: Supplementary File S5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in T3M-4 cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S8 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S8 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in SJSA-1 cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 KO_p53i cells induced with doxycycline (50 ng/ml) vs. PBS control (12.5 h).
View article: Supplementary File S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 KO cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S11 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S11 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
The restoration of WT p53 transcriptional responses by PC14586 in p53-Y220C–expressing cells (NUGC-3 and T3M-4) at 5 and 16 h was assessed through GSEA analysis for DEGs.
View article: Figure 6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Responses of two patients with solid tumors harboring TP53 Y220C mutations receiving rezatapopt. A–C Patient with advanced small cell lung carcinoma from the PYNNACLE phase I study. A, CT scans at baseline and 12 weeks…
View article: Supplementary File S1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 cells treated by PC14586 (5 µM) vs. DMSO control (16 h).