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Articles by de Stanchina
FET Fusion Oncoproteins Disrupt Physiologic DNA Repair and Create a Targetable Opportunity for ATR Inhibitor Therapy Open Access
Open figure viewer The DNA damage response (DDR) is a tightly regulated and redundant network that tailors specific repair complexes to address a diverse set of genotoxic insults. In cancer, oncogene-induced hyperproliferation and replication stress (RS) activate the DDR which can trigger senescence or cell death programs (1).
FET Fusion Oncoproteins Disrupt Physiologic DNA Repair and Create a Targetable Opportunity for ATR Inhibitor Therapy Open Access
Open figure viewer This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .
Trastuzumab Deruxtecan Resistance via Loss of HER2 Expression and Binding
Antibody–drug conjugates (ADC) represent a groundbreaking class of therapeutic agents that are designed to combine the specificity of antibodies with the efficacy of chemotherapy. These complex molecules consist of a mAb targeting tumor-specific antigens, a cytotoxic payload to eliminate cancer cells, and a linker that connects them.
RRAS and RRAS2 mutations are recurrent oncogenic drivers in lung cancer and are sensitive to the pan-RAS inhibitor RMC-6236
Introduction: RRAS and RRAS2 encode a subfamily of RAS-like small GTPases that share considerable structural and functional similarities with KRAS, HRAS, and NRAS. Whether homologous RRAS/RRAS2 mutations are oncogenic and actionable drivers in lung cancer remains underexplored. Methods: An institutional cohort of 8,488 non-small cell lung carcinomas (NSCLC) sequenced by comprehensive targeted DNA sequencing (MSK-IMPACT) between 2016-2024 was evaluated for RRAS/RRAS2 mutations.
Sensitivity of metastatic mucinous tailgut cyst adenocarcinoma to gemcitabine and radiation: a case report
Introduction Tailgut cyst or retrorectal cyst hamartoma is a congenital remnant of the embryonic tailgut (1). The developing human embryo has a tail caudal to the cloaca (future anorectal canal), and a portion of the hindgut extends into this tail as the tailgut or post-anal gut (Supplementary Figure S1) (2). Failure of the tailgut to involute by the eighth week of gestation can result in cysts.
Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations That Overcome Its Feedback Inhibition of RAC1 and Migration
Mutations that activate ERK signaling are drivers of a substantial fraction of human cancers. The most prevalent BRAF mutants, V600 alleles, have extremely high kinase activity (1) and ERK transcriptional output with concomitant marked ERK-dependent feedback inhibition of upstream signaling (2). BRAF mutants are common in melanomas, thyroid, and colorectal carcinomas. Proliferation of these tumors is sensitive to ERK inhibition by MEK or RAF inhibitors and ablation of the BRAFV600E allele (3–5).
Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations that Overcome it’s Feedback Inhibition of RAC1 and Migration
This content is only available via PDF. This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .
HER2 antibody-drug conjugates are active against desmoplastic small round cell tumor
Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare but highly aggressive soft tissue sarcoma that arises in the abdominopelvic cavity of young males. Since the discovery of EWSR1::WT1 fusion as the driver of DSRCT, no actionable genomic alterations have been identified, limiting disease management to a combination of surgery, chemotherapy, and radiation with very poor outcomes. Herein, we leveraged ERBB2/HER2 expression in DSRCT as a therapeutic target.
Heterodimerization of T cell engaging bispecific antibodies to enhance specificity against pancreatic ductal adenocarcinoma - Journal of Hematology & Oncology
Abstract EGFR and/or HER2 expression in pancreatic cancers is correlated with poor prognoses. We generated homodimeric (EGFRxEGFR or HER2xHER2) and heterodimeric (EGFRxHER2) T cell-engaging bispecific antibodies (T-BsAbs) to direct polyclonal T cells to these antigens on pancreatic tumors.
De novo and histologically transformed small cell lung cancer is sensitive to lurbinectedin treatment through the modulation of EMT and NOTCH signaling pathways.
Purpose: Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor with dismal prognosis and limited treatment options. Lurbinectedin, conditionally approved as a second-line treatment for metastatic SCLC, drives clinical responses in about 35% of patients and the overall survival of those who benefit from it remains very low (~9.3 months). This highlights the need to develop improved mechanistic insight and predictive biomarkers of response.
Synthetic lethality of drug-induced polyploidy and BCL-2 inhibition in lymphoma
Nature Communications, Apr 2023 This is a preview of a remote PDF: https://www.nature.com/articles/s41467-023-37216-2.pdf Portelinha, Ana, da Silva Ferreira, Mariana, Erazo, Tatiana, Jiang, Man, Asgari, Zahra, de Stanchina, Elisa, Younes, Anas, Wendel, Hans-Guido. , Nature Communications, DOI: 10.1038/s41467-023-37216-2
Inducible expression of interleukin-12 augments the efficacy of affinity-tuned chimeric antigen receptors in murine solid tumor models
Nature Communications, Apr 2023 This is a preview of a remote PDF: https://www.nature.com/articles/s41467-023-37646-y.pdf Yang, Yanping, Yang, Huan, Alcaina, Yago, Puc, Janusz, Birt, Alyssa, Vedvyas, Yogindra, Gallagher, Michael, Alla, Srinija, Riascos, Maria Cristina, McCloskey, Jaclyn E., Du, Karrie, Gonzalez-Valdivieso, Juan, Min, Irene M., de Stanchina, Elisa, Britz, Matt, von Hofe, Eric, Jin, Moonsoo M.. , Nature Communications, DOI: 10.1038/s41467-023-37646-y
Antitumor activity of the PI3K δ-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer
Breast Cancer Research and Treatment, Mar 2023 This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1007/s10549-023-06895-2.pdf Fiascarelli, Alessio, Merlino, Giuseppe, Capano, Stefania, Talucci, Simone, Bisignano, Diego, Bressan, Alessandro, Bellarosa, Daniela, Carrisi, Corrado, Paoli, Alessandro, Bigioni, Mario, Tunici, Patrizia, Irrissuto, Clelia, Salerno, Massimiliano, Arribas, Joaquin, de Stanchina, Elisa, Scaltriti, Maurizio, Binaschi, Monica.
Genomic and transcriptomic analysis of a diffuse pleural mesothelioma patient-derived xenograft library - Genome Medicine
Patient samples and clinical annotation All human tissue obtained for PDX generation was from patients with a diagnosis of DPM who gave informed consent on an IRB-approved protocol at Memorial Sloan Kettering Cancer Center (MSK). All study procedures were conducted in accordance with the US Common Rule which is an ethical standard established for conduct of any US government-funded research.
Diverse alterations associated with resistance to KRAS(G12C) inhibition - Nature
Abstract Inactive state-selective KRAS(G12C) inhibitors1,2,3,4,5,6,7,8 demonstrate a 30–40% response rate and result in approximately 6-month median progression-free survival in patients with lung cancer9. The genetic basis for resistance to these first-in-class mutant GTPase inhibitors remains under investigation. Here we evaluated matched pre-treatment and post-treatment specimens from 43 patients treated with the KRAS(G12C) inhibitor sotorasib.
Tumor-targeted nanoparticles improve the therapeutic index of BCL2 and MCL1 dual inhibition
Skip Nav Destination Lymphoid Neoplasia| April 15, 2021 You do not currently have access to this content. Sign in via your Institution
Tumor Targeted Nanoparticles Improve Therapeutic Index of BCL2 and MCL1 dual inhibition
Skip Nav Destination Research Article| October 16, 2020 You do not currently have access to this content.
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