A NEW PARADIGM FOR TARGETING MUTANT P53 TUMOURS
Grant number: 1120293 | Funding period: 2017 - 2020
Over half of all cancers contain mutations in a gene called TP53, also known as the “guardian of the genome”. Mutation of TP53 provides tumour cells with a growth advantage, and leads to resistance to chemotherapy and poor outcomes for patients. We have identified a potential “Achilles heel” in cancers with TP53 mutations. In this project we will establish a new paradigm for treating tumours with TP53 mutations that will be applicable to a large number of patients across all types of cancer.
Related publications (8)
SLC7A11 Is a Superior Determinant of APR-246 (Eprenetapopt) Response than TP53 Mutation Status
Kenji M Fujihara, Mariana Corrales Benitez, Carlos S Cabalag, Bonnie Z Zhang, Hyun S Ko, David S Liu, Kaylene J Simpson, Ygal Haupt, Lara Lipton, Sue Haupt, Wayne A Phillips, Nicholas J Clemons
APR-246 (eprenetapopt) is in clinical development with a focus on hematologic malignancies and is promoted as a mutant-p53 reactiv..
Transketolase regulates sensitivity to APR-246 in p53-null cells independently of oxidative stress modulation
Julia Milne, Bonnie Z Zhang, Kenji M Fujihara, Swati Dawar, Wayne A Phillips, Nicholas J Clemons
The prevalence and dire implications of mutations in the tumour suppressor, p53, highlight its appeal as a chemotherapeutic target..
Loss of SMAD4 Is Sufficient to Promote Tumorigenesis in a Model of Dysplastic Barrett's Esophagus
Jovana R Gotovac, Tanjina Kader, Julia Milne, Kenji M Fujihara, Luis E Lara-Gonzalez, Kylie L Gorringe, Sangeetha N Kalimuthu, Madawa W Jayawardana, Cuong P Duong, Wayne A Phillips, Nicholas J Clemons
BACKGROUND & AIMS: Esophageal adenocarcinoma (EAC) develops from its precursor Barrett's esophagus through intermediate stages of ..
A thiol-bound drug reservoir enhances APR-246-induced mutant p53 tumor cell death
Sophia Ceder, Sofi E Eriksson, Emarndeena H Cheteh, Swati Dawar, Mariana Corrales Benitez, Vladimir JN Bykov, Kenji M Fujihara, Melodie Grandin, Xiaodun Li, Susanne Ramm, Corina Behrenbruch, Kaylene J Simpson, Frederic Hollande, Lars Abrahmsen, Nicholas J Clemons, Klas G Wiman
The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is co..
GRB7 is an oncogenic driver and potential therapeutic target in oesophageal adenocarcinoma
Jovana R Gotovac, David SH Liu, Michael J Yates, Julia Milne, Arthi A Macpherson, Kaylene J Simpson, Guy D Eslick, Catherine Mitchell, Cuong P Duong, Wayne A Phillips, Nicholas J Clemons
Efficacious therapeutic approaches are urgently needed to improve outcomes in patients with oesophageal adenocarcinoma (OAC). Howe..
Inhibiting the system x((C)over-bar)/glutathione axis selectively targets cancers with mutant-p53 accumulation
David S Liu, Cuong P Duong, Sue Haupt, Karen G Montgomery, Colin M House, Walid J Azar, Helen B Pearson, Oliver M Fisher, Matthew Read, Glen R Guerra, Ygal Haupt, Carleen Cullinane, Klas G Wiman, Lars Abrahmsen, Wayne A Phillips, Nicholas J Clemons
TP53, a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and p..
Inhibiting system x(C)(-) and glutathione biosynthesis - a potential Achilles' heel in mutant-p53 cancers
Nicholas J Clemons, David S Liu, Cuong P Duong, Wayne A Phillips
Effective therapeutic strategies to target mutant tumor protein p53 (TP53, best known as p53) cancers remain an unmet medical need..