ONCOGENIC SIGNALING AND CANCER THERAPY

Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway

Katherine M Hannan, Priscilla Soo, Mei S Wong, Justine K Lee, Nadine Hein, Perlita Poh, Kira D Wysoke, Tobias D Williams, Christian Montellese, Lorey K Smith, Sheren J Al-Obaidi, Lorena Nunez-Villacis, Megan Pavy, Jin-Shu He, Kate M Parsons, Karagh E Loring, Tess Morrison, Jeannine Diesch, Gaetan Burgio, Rita Ferreira

2022-11-01

The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal..

Clinical validation and implementation of droplet digital PCR for the detection of BRAF mutations from cell-free DNA

Rainer Arnolda, Kerry Howlett, Timmy Chan, Jeanette Raleigh, Athena Hatzimihalis, Anthony Bell, Andrew Fellowes, Shahneen Sandhu, Grant A Mcarthur, Stephen B Fox, Sarah-jane Dawson, Chelsee Hewitt, Kate Jones, Stephen Q Wong

2022-10-01

Droplet digital PCR (ddPCR) has been demonstrated in many research studies to be a sensitive method in the analysis of circulating..

Cystathionine-beta-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation

Haoran Zhu, Keefe T Chan, Xinran Huang, Carmelo Cerra, Shaun Blake, Anna S Trigos, Dovile Anderson, Darren J Creek, David P De Souza, Xi Wang, Caiyun Fu, Metta Jana, Elaine Sanij, Richard B Pearson, Jian Kang

2022-06-27

Hyperactivation of oncogenic pathways downstream of RAS and PI3K/AKT in normal cells induces a senescence-like phenotype that acts..

Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAF(V600) melanoma

Lorey K Smith, Tiffany Parmenter, Margarete Kleinschmidt, Eric P Kusnadi, Jian Kang, Claire A Martin, Peter Lau, Riyaben Patel, Julie Lorent, David Papadopoli, Anna Trigos, Teresa Ward, Aparna D Rao, Emily J Lelliott, Karen E Sheppard, David Goode, Rodney J Hicks, Tony Tiganis, Kaylene J Simpson, Ola Larsson

2022-03-01

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately ..

The therapeutic potential of RNA Polymerase I transcription inhibitor, CX-5461, in uterine leiomyosarcoma

Chang-Won Kang, Katherine M Hannan, Anneke C Blackburn, Amos HP Loh, Kuick Chik Hong, Goh Jian Yuan, Nadine Hein, Denis Drygin, Ross D Hannan, Lucy A Coupland

2022-02-24

BACKGROUND: Uterine leiomyosarcoma is a rare aggressive smooth muscle cancer with poor survival rates. RNA Polymerase I (Pol I) ac..

Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

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

2021-08-30

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

Impaired ribosome biogenesis checkpoint activation induces p53-dependent MCL-1 degradation and MYC-driven lymphoma death

Ana Domostegui, Suresh Peddigari, Carol A Mercer, Flavia Iannizzotto, Marta L Rodriguez, Marta Garcia-Cajide, Virginia Amador, Sarah T Diepstraten, Gemma L Kelly, Ramon Salazar, Sara C Kozma, Eric P Kusnadi, Jian Kang, Antonio Gentilella, Richard B Pearson, George Thomas, Joffrey Pelletier

2021-06-17

MYC-driven B-cell lymphomas are addicted to increased levels of ribosome biogenesis (RiBi), offering the potential for therapeutic..

Circulating Tumor DNA Predicts Outcome from First-, but not Second-line Treatment and Identifies Melanoma Patients Who May Benefit from Combination Immunotherapy

Gabriela Marsavela, Jenny Lee, Leslie Calapre, Stephen Q Wong, Michelle R Pereira, Ashleigh C McEvoy, Anna L Reid, Cleo Robinson, Lydia Warburton, Afaf Abed, Muhammad A Khattak, Tarek M Meniawy, Sarah-Jane Dawson, Shahneen Sandhu, Matteo S Carlino, Alexander M Menzies, Richard A Scolyer, Georgina Long, Benhur Amanuel, Michael Millward

2020-11-15

PURPOSE: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melano..

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

2020-11-02

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

Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAF(V600) melanoma cells

Lorey K Smith, Tiffany Parmenter, Cathryn M Gould, Piyush B Madhamshettiwar, Karen E Sheppard, Kaylene J Simpson, Grant A McArthur

2020-10-12

Identification of mechanisms underlying sensitivity and response to targeted therapies, such as the BRAF inhibitor vemurafenib, is..

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

2020-05-26

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

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

2020-02-01

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

Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload

Chentao Ge, Hemiao Huang, Feiyan Huang, Tianxin Yang, Tengfei Zhang, Hongzhang Wu, Hanwei Zhou, Qi Chen, Yue Shi, Yanfang Sun, Liangjue Liu, Xi Wang, Richard B Pearson, Yihai Cao, Jian Kang, Caiyun Fu

2019-09-24

Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-..

Somatic mutations in early metazoan genes disrupt regulatory links between unicellular and multicellular genes in cancer

Anna S Trigos, Richard B Pearson, Anthony T Papenfuss, David L Goode

2019-02-26

Extensive transcriptional alterations are observed in cancer, many of which activate core biological processes established in unic..

Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation

Jeannine Diesch, Megan J Bywater, Elaine Sanij, Donald P Cameron, William Schierding, Natalie Brajanovski, Jinbae Son, Jirawas Sornkom, Nadine Hein, Maurits Evers, Richard B Pearson, Grant A McArthur, Austen RD Ganley, Justin M O'Sullivan, Ross D Hannan, Gretchen Poortinga

2019-01-28

The three-dimensional organization of the genome contributes to its maintenance and regulation. While chromosomal regions associat..

High-Content Imaging Approaches to Quantitate Stress-Induced Changes in Nucleolar Morphology

Jin-Shu He, Priscilla Soo, Maurits Evers, Kate M Parsons, Nadine Hein, Katherine M Hannan, Ross D Hannan, Amee J George

2018-08-01

The nucleolus is a dynamic subnuclear compartment that has a number of different functions, but its primary role is to coordinate ..

Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers

Maheshi Udugama, Elaine Sanij, Hsiao PJ Voon, Jinbae Son, Linda Hii, Jeremy D Henson, F Lyn Chan, Fiona TM Chang, Yumei Liu, Richard B Pearson, Paul Kalitsis, Jeffrey R Mann, Philippe Collas, Ross D Hannan, Lee H Wong

2018-05-01

ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochr..

How the evolution of multicellularity set the stage for cancer

Anna S Trigos, Richard B Pearson, Anthony T Papenfuss, David L Goode

2018-01-23

Neoplastic growth and many of the hallmark properties of cancer are driven by the disruption of molecular networks established dur..

Does addition of a diagnostic contrast-enhanced CT to a contemporaneous PET/CT provide incremental value in patients for restaging of colorectal carcinoma?

Kenneth SK Yap, Ojas H Mehta, Wing Fai Eddie Lau, Tim Akhurst, Satish Warrier, Alexander Heriot, Rodney J Hicks

2018-01-01

Background: Both constrast-enhanced computed tomography (ceCT) and 18F-Fluorodeoxyglucose positron emission tomography (PET) are w..

TERT structural rearrangements in metastatic pheochromocytomas

Trisha Dwight, Aidan Flynn, Kaushalya Amarasinghe, Diana E Benn, Richard Lupat, Jason Li, Daniel L Cameron, Annette Hogg, Shiva Balachander, Ida LM Candiloro, Stephen Q Wong, Bruce G Robinson, Anthony T Papenfuss, Anthony J Gill, Alexander Dobrovic, Rodney J Hicks, Roderick J Clifton-Bligh, Richard W Tothill

2018-01-01

Pheochromocytomas (PC) and paragangliomas (PGL) are endocrine tumors for which the genetic and clinicopathological features of met..

Inhibition of Pol I Transcription a New Chance in the Fight Against Cancer

Nadine Hein, Kathrine M Hannan, James D'Rozario, Ross Hannan

2017-12-01

While new cancer treatments continue to improve patient outcomes, for some cancers there have been limited or no improvements for ..

Seduction by Sensitivity: Reality, Illusion, or Delusion? The Challenge of Assessing Outcomes after PSMA Imaging Selection of Patients for Treatment

Rodney J Hicks, Declan G Murphy, Scott G Williams

2017-12-01

The Advantages and Challenges of Using FDG PET/CT for Response Assessment in Melanoma in the Era of Targeted Agents and Immunotherapy

Annie NM Wong, Grant A McArthur, Michael S Hofman, Rodney J Hicks

2017-08-01

The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of thi..

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

Anna S Trigos, Richard B Pearson, Anthony T Papenfuss, David L Goode

2017-06-13

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained prolifera..

Inhibition of Pol I transcription treats murine and human AML by targeting the leukemia-initiating cell population

Nadine Hein, Donald P Cameron, Katherine M Hannan, Nhu-Y N Nguyen, Chun Yew Fong, Jirawas Sornkom, Meaghan Wall, Megan Pavy, Carleen Cullinane, Jeannine Diesch, Jennifer R Devlin, Amee J George, Elaine Sanij, Jaclyn Quin, Gretchen Poortinga, Inge Verbrugge, Adele Baker, Denis Drygin, Simon J Harrison, James D Rozario

2017-05-25

Despite the development of novel drugs, the prospects for many patients with acute myeloid leukemia (AML) remain dismal. This stud..

Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription

Sandy S Hung, Analia Lesmana, Abigail Peck, Rachel Lee, Elly Tchoubrieva, Katherine M Hannan, Jane Lin, Karen E Sheppard, Katarzyna Jastrzebski, Leonie M Quinn, Lawrence I Rothblum, Richard B Pearson, Ross D Hannan, Elaine Sanij

2017-05-15

Transcription of the ribosomal RNA genes (rDNA) by RNA polymerase I (Pol I) is a major control step for ribosome synthesis and is ..

Selective inhibition of RNA polymerase I transcription as a potential approach to treat African trypanosomiasis

Louise E Kerry, Elaine E Pegg, Donald P Cameron, James Budzak, Gretchen Poortinga, Katherine M Hannan, Ross D Hannan, Gloria Rudenko

2017-03-01

Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High ..

Therapeutic Approaches Targeting MYC-Driven Prostate Cancer

Richard J Rebello, Richard B Pearson, Ross D Hannan, Luc Furic

2017-02-01

The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also in..

Circulating Tumor DNA Analysis and Functional Imaging Provide Complementary Approaches for Comprehensive Disease Monitoring in Metastatic Melanoma

Stephen Q Wong, Jeanette M Raleigh, Jason Callahan, Ismael A Vergara, Sarah Ftouni, Athena Hatzimihalis, Andrew J Colebatch, Jason Li, Timothy Semple, Kenneth Doig, Christopher Mintoff, Devbarna Sinha, Paul Yeh, Maria Joao Silva, Kathryn Alsop, Heather Thorne, David D Bowtell, David E Gyorki, Gisela Mir Arnau, Carleen Cullinane

2017-01-01

PURPOSE: Circulating tumor DNA (ctDNA) allows noninvasive disease monitoring across a range of malignancies. In metastatic melanom..

The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

Shunfei Yan, Daniel Frank, Jinbae Son, Katherine M Hannan, Ross D Hannan, Keefe T Chan, Richard B Pearson, Elaine Sanij

2017-01-01

Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options ar..

The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer

Richard J Rebello, Eric Kusnadi, Donald P Cameron, Helen B Pearson, Analia Lesmana, Jennifer R Devlin, Denis Drygin, Ashlee K Clark, Laura Porter, John Pedersen, Shahneen Sandhu, Gail P Risbridger, Richard B Pearson, Ross D Hannan, Luc Furic

2016-11-15

PURPOSE: The MYC oncogene is frequently overexpressed in prostate cancer. Upregulation of ribosome biogenesis and function is char..

Clustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies

Andrew J Colebatch, Leon Di Stefano, Stephen Q Wong, Ross D Hannan, Paul M Waring, Alexander Dobrovic, Grant A McArthur, Anthony T Papenfuss

2016-10-11

Most cancer DNA sequencing studies have prioritized recurrent non-synonymous coding mutations in order to identify novel cancer-re..

Combining High-Content Imaging and Phenotypic Classification Analysis of Senescence-Associated Beta-Galactosidase Staining to Identify Regulators of Oncogene-Induced Senescence

Keefe T Chan, Lassi Paavolainen, Katherine M Hannan, Amee J George, Ross D Hannan, Kaylene J Simpson, Peter Horvath, Richard B Pearson

2016-09-01

Hyperactivation of the PI3K/AKT/mTORC1 signaling pathway is a hallmark of the majority of sporadic human cancers. Paradoxically, c..

Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription

Jian Kang, Eric P Kusnadi, Allison J Ogden, Rodney J Hicks, Lukas Bammert, Ulrike Kutay, Sandy Hung, Elaine Sanij, Ross D Hannan, Katherine M Hannan, Richard B Pearson

2016-08-02

Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transf..

Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling

Jaclyn Quin, Keefe T Chan, Jennifer R Devlin, Donald P Cameron, Jeannine Diesch, Carleen Cullinane, Jessica Ahern, Amit Khot, Nadine Hein, Amee J George, Katherine M Hannan, Gretchen Poortinga, Karen E Sheppard, Kum Kum Khanna, Ricky W Johnstone, Denis Drygin, Grant A McArthur, Richard B Pearson, Elaine Sanij, Ross D Hannan

2016-08-02

RNA polymerase I (Pol I)-mediated transcription of the ribosomal RNA genes (rDNA) is confined to the nucleolus and is a rate-limit..

Desmoglein 2 promotes vasculogenic mimicry in melanoma and is associated with poor clinical outcome

Lih Yin Tan, Chris Mintoff, M Zahied Johan, Brenton W Ebert, Clare Fedele, You Fang Zhang, Pacman Szeto, Karen E Sheppard, Grant A McArthur, Erwin Foster-Smith, Andrew Ruszkiewicz, Michael P Brown, Claudine S Bonder, Mark Shackleton, Lisa M Ebert

2016-07-19

Tumors can develop a blood supply not only by promoting angiogenesis but also by forming vessel-like structures directly from tumo..

Combination Therapy Targeting Ribosome Biogenesis and mRNA Translation Synergistically Extends Survival in MYC-Driven Lymphoma

Jennifer R Devlin, Katherine M Hannan, Nadine Hein, Carleen Cullinane, Eric Kusnadi, Pui Yee Ng, Amee J George, Jake Shortt, Megan J Bywater, Gretchen Poortinga, Elaine Sanij, Jian Kang, Denis Drygin, Sean O'Brien, Ricky W Johnstone, Grant A McArthur, Ross D Hannan, Richard B Pearson

2016-01-01

UNLABELLED: Ribosome biogenesis and protein synthesis are dysregulated in many cancers, with those driven by the proto-oncogene c-..

Regulation of rDNA transcription in response to growth factors, nutrients and energy

Eric P Kusnadi, Katherine M Hannan, Rodney J Hicks, Ross D Hannan, Richard B Pearson, Jian Kang

2015-02-01

Exquisite control of ribosome biogenesis is fundamental for the maintenance of cellular growth and proliferation. Importantly, syn..

Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma

SQ Wong, A Behren, VJ Mar, K Woods, J Li, C Martin, KE Sheppard, R Wolfe, J Kelly, J Cebon, A Dobrovic, GA McArthur

2015-01-20

Melanoma is often caused by mutations due to exposure to ultraviolet radiation. This study reports a recurrent somatic C > T chang..

Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma

Victoria J Mar, Stephen Q Wong, Aleksandra Logan, Nguyen Trung, Jonathan Cebon, John W Kelly, Rory Wolfe, Alexander Dobrovic, Catriona McLean, Grant A McArthur

2014-11-01

Activating mutations in the GTPase RAC1 are a recurrent event in cutaneous melanoma. We investigated the clinical and pathological..