PRE-CLINICAL EVALUATION OF THE LSD1 INHIBITOR HCI-2509: DEFINING THE BIOMARKERS OF SENSITIVITY AND THE MECHANISMS OF RESISTANCE

Grant number: 1111032 | Funding period: 2018 - 2020

Completed

Abstract

Despite aggressive multi-modal treatment strategies, limited progress in the treatment of Ewing sarcoma (paediatric bone malignancy), has been achieved over the past 30 years. As such, the advent of novel and targeted therapeutics with favourable efficacy/toxicity profiles are eagerly awaited. This proposal will investigate the therapeutic utility of LSD1 inhibition as a treatment for Ewing sarcoma and the underlying mechanisms of sensitivity/resistance to this unique agent.

Related publications (5)

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Mitochondrial Dysfunction Is a Driver of SP-2509 Drug Resistance in Ewing Sarcoma.

E John Tokarsky, Jesse C Crow, Lillian M Guenther, John Sherman, Cenny Taslim, Gabriela Alexe, Kathleen I Pishas, Galen Rask, Blake S Justis, Ana Kasumova, Kimberly Stegmaier, Stephen L Lessnick, Emily R Theisen

2022-07-06

UNLABELLED: Expression of the fusion oncoprotein EWS/FLI causes Ewing sarcoma, an aggressive pediatric tumor characterized by wide..

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Phenotypic Consequences of SLC25A40-ABCB1 Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer

Kathleen Pishas, Karla J Cowley, Ahwan Pandey, Therese Hoang, Jessica A Beach, Jennii Luu, Robert Vary, Lorey K Smith, Carolyn E Shembrey, Nineveh Rashoo, Madelynne O White, Kaylene J Simpson, Andrea Bild, Jason Griffiths, Dane Cheasley, Ian Campbell, David DL Bowtell, Elizabeth L Christie

2021-11-01

Despite high response rates to initial chemotherapy, the majority of women diagnosed with High-Grade Serous Ovarian Cancer (HGSOC)..

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Network potential identifies therapeutic miRNA cocktails in Ewing sarcoma.

Davis T Weaver, Kathleen I Pishas, Drew Williamson, Jessica Scarborough, Stephen L Lessnick, Andrew Dhawan, Jacob G Scott

2021-10-01

MicroRNA (miRNA)-based therapies are an emerging class of targeted therapeutics with many potential applications. Ewing Sarcoma pa..

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Chromatin profiling reveals relocalization of lysine-specific demethylase 1 by an oncogenic fusion protein.

Emily R Theisen, Julia Selich-Anderson, Kyle R Miller, Jason M Tanner, Cenny Taslim, Kathleen I Pishas, Sunil Sharma, Stephen L Lessnick

2021-04-01

Paediatric cancers commonly harbour quiet mutational landscapes and are instead characterized by single driver events such as the ..

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The development of drug resistance through reversion mutation in BRCA genes in ovarian cancer

EL Christie, AE Freimund, S Fereday, K Alsop, T Hoang, K Pishas, G Au-Yeung, M Friedlander, DD Bowtell

2020-01-01

BRCA1 and BRCA2 tumor suppressor genes are central components of the homologous recombination (HR) DNA repair pathway, a high-fide..