Keefe Chan

Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

Jian Kang, Natalie Brajanovski, Keefe T Chan, Jiachen Xuan, Richard B Pearson, Elaine Sanij

Journal article  |  2021  |  SIGNAL TRANSDUCTION AND TARGETED THERAPY

Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth and proliferation. The ribosomal pro..

The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer

Shunfei Yan, Jiachen Xuan, Natalie Brajanovski, Madeleine RC Tancock, Piyush B Madhamshettiwar, Kaylene J Simpson, Sarah Ellis, Jian Kang, Carleen Cullinane, Karen E Sheppard, Katherine M Hannan, Ross D Hannan, Elaine Sanij, Richard B Pearson, Keefe T Chan

Journal article  |  2020  |  BRITISH JOURNAL OF CANCER

BACKGROUND: Intrinsic and acquired drug resistance represent fundamental barriers to the cure of high-grade serous ovarian carcino..

Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis

Eric P Kusnadi, Anna S Trigos, Carleen Cullinane, David L Goode, Ola Larsson, Jennifer R Devlin, Keefe T Chan, David P De Souza, Malcolm J McConville, Grant A McArthur, George Thomas, Elaine Sanij, Gretchen Poortinga, Ross D Hannan, Katherine M Hannan, Jian Kang, Richard B Pearson

Journal article  |  2020  |  EMBO JOURNAL

Elevated ribosome biogenesis in oncogene-driven cancers is commonly targeted by DNA-damaging cytotoxic drugs. Our previous first-i..

Inhibition of RNA polymerase I transcription activates targeted DNA damage response and enhances the efficacy of PARP inhibitors in high-grade serous ovarian cancer.

Elaine Sanij, Katherine Hannan, Jiachen Xuan, Shunfei Yan, Jessica A Ahern, Anna S Trigos, Natalie Brajanovski, Jinbae Son, Keefe T Chan, Olga Kondrashova, Elizabeth Lieschke, Matthew J Wakefield, Sarah Ellis, Carleen Cullinane, Gretchen Poortinga, Kum Kum Khanna, Linda Mileshkin, Grant A McArthur, John Soong, Els M Berns, et al.

Conference Proceedings  |  2020  |  CLINICAL CANCER RESEARCH

CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer

Elaine Sanij, Katherine M Hannan, Jiachen Xuan, Shunfei Yan, Jessica E Ahern, Anna S Trigos, Natalie Brajanovski, Jinbae Son, Keefe T Chan, Olga Kondrashova, Elizabeth Lieschke, Matthew J Wakefield, Daniel Frank, Sarah Ellis, Carleen Cullinane, Jian Kang, Gretchen Poortinga, Purba Nag, Andrew J Deans, Kum Kum Khanna, et al.

Journal article  |  2020  |  NATURE COMMUNICATIONS

Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the clinical management of high grade serous ovarian cance..

Oncogene-induced senescence: From biology to therapy

Haoran Zhu, Shaun Blake, Frances K Kusuma, Richard B Pearson, Jian Kang, Keefe T Chan

Journal article  |  2020  |  MECHANISMS OF AGEING AND DEVELOPMENT

Oncogene-induced senescence (OIS) is a powerful intrinsic tumor-suppressive mechanism, arresting cell cycle progression upon oncog..

A functional genetic screen defines the AKT-induced senescence signaling network

Keefe T Chan, Shaun Blake, Haoran Zhu, Jian Kang, Anna S Trigos, Piyush B Madhamshettiwar, Jeannine Diesch, Lassi Paavolainen, Peter Horvath, Ross D Hannan, Amee J George, Elaine Sanij, Katherine M Hannan, Kaylene J Simpson, Richard B Pearson

Journal article  |  2020  |  Cell Death and Differentiation

Exquisite regulation of PI3K/AKT/mTORC1 signaling is essential for homeostatic control of cell growth, proliferation, and survival..

Targeting RNA Polymerase I transcription synergises with TOP1 inhibition in potentiating the DNA damage response in high-grade serous ovarian cancer

Shunfei Yan, Piyush Madhamshettiwar, Kaylene Simpson, Sarah Ellis, Jian Kang, Carleen Cullinane, Karen Sheppard, Katherine Hannan, Ross Hannan, Elaine Sanij, Richard Pearson, Keefe Chan

Journal article  |  2019

Limited effective therapeutic options are available for patients with recurrent high-grade serous carcinoma (HGSC), the most commo..

Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis

EP Kusnadi, AS Trigos, C Cullinane, DL Goode, O Larsson, JR Devlin, KT Chan, DP De Souza, MJ McConville, GA McArthur, G Thomas, E Sanij, G Poortinga, RD Hannan, KM Hannan, J Kang, RB Pearson

Journal article  |  2019

Elevated ribosome biogenesis in oncogene-driven cancers is commonly targeted by DNA-damaging cytotoxic drugs. Our first-in-human t..

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

Shatha AbuHammad, Carleen Cullinane, Claire Martin, Zoe Bacolas, Teresa Ward, Huiqin Chen, Alison Slater, Kerry Ardley, Laura Kirby, Keefe T Chan, Natalie Brajanovski, Lorey K Smith, Aparna D Rao, Emily J Lelliott, Margarete Kleinschmidt, Ismael A Vergara, Anthony T Papenfuss, Peter Lau, Prerana Ghosh, Sue Haupt, et al.

Journal article  |  2019  |  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor-positive breast cancer and are c..