Publish Date: 
Thursday, May 13, 2021 - 09:00

Artificial intelligence opening new fields for cancer researchers

Genomic researchers at the Translational Research Institute are using artificial intelligence (AI) to discover potential new therapeutics for cancer.

Led by the Queensland University of Technology’s (QUT) Dr Pascal Duijf (pictured right), the scientists plan to investigate new treatments for several different cancers they unearthed using artificial intelligence.

Within the School of Biomedical Sciences at QUT, Dr Duijf is also leading research projects to help clinicians diagnose cancers in patients.

“My research focusses on identifying the mechanisms that underlie genomic instability in cancer cells, and on how we can utilise genomic changes to benefit cancer patients in terms of diagnostics and therapeutics,” says Dr Duijf.

Potential new cancer treatments thanks to AI

Combining AI with large cancer patient data sets is one of Dr Duijf’s key interests, and it has helped his research group identify a wide range of potential new opportunities to improve therapeutics and treatment approaches for cancer patients.

“While we use various different approaches and methods in our research, artificial intelligence and advanced statistical methods have recently become more prominent,” he said.

“This is an area that I’m really excited about and that is also why I recently joined the Centre for Data Science at QUT.”

In a groundbreaking study published in 2020 in Nature Communications, Dr Duijf, Ankit Shukla from The University of Queensland Diamantina Institute, and their collaborators used statistics and artificial intelligence to analyse chromosome arm abnormalities in more than 23,000 human tumours and 1000 cancer cell lines.

According to Dr Duijf, the team identified a wide range of new opportunities with the potential to improve therapeutics and personalised treatment approaches for cancer patients.

“One of the things that we found was that there are specific chromosomal arm gains and losses in tumours, which can sensitise cancer cells to chemotherapies,” he said.

"We used artificial intelligence to identify 31 chromosome arm gains or losses that profoundly change the response of cancer cells to 56 different therapeutics."

While the drugs now need to be tested extensively in a laboratory setting to confirm their use in treating the cancers, Dr Duijf says the discovery is nonetheless exciting for its research translation possibilities in patients.

“The drugs that we identified are all existing therapeutics, and quite a number of them have been previously used, in some cases to treat other cancers, but in many cases for other diseases,” he said.

“For example, one of the drugs has been used to treat neurological diseases that do not relate to cancer. Taking an existing drug to treat other diseases, and in this case to treat cancer, is known as drug repurposing. A great benefit of this is that we know the drug is safe to use in patients, the dose to use, and often the side effects and how to manage those side effects. This is a great benefit for clinical trials, because you can essentially skip the first stage and trial the therapy in larger patient cohorts.”

The researchers identified therapeutics for 17 cancer types, but they initially plan to continue their studies into two different cancer types. They will test the potential therapies in laboratory-based studies before moving into patient studies in several years’ time.

Predicting cancer spread in patients

Driven by Ankit Shukla, Dr Duijf and his team are also looking at gains and losses of chromosome arms in tumours at primary and metastatic cancer sites to help understand and predict how cancers will develop in patients.

The loss or gain of chromosomal arms in cancer cells occur frequently, in 90% of all cancers, especially as the tumours develop over time and become progressively more malignant, according to Dr Duijf.

“Normally, a cancer develops in a certain organ, for example the breast, brain or lung, and we call that the primary site. Then it might develop over time, accumulating more abnormalities, with the cells eventually leaving this primary site and spreading through the body, which we call metastasis.”

“This process of ongoing development of the cancer cells and their progressively becoming more malignant is what we refer to as tumour evolution.”

The work by Dr Duijf and his team may help predict to which metastatic site or organ a primary breast, prostate and some other cancers will potentially spread.

“We have discovered aspects of tumour evolution through this research and I’m very excited about its potential implications for patients. There’s still a long way to go from our primary research finding to a translational outcome, but this is a very promising observation.”

Importance of the TRI to research

Dr Duijf moved to Australia in 2013, so that he could base his research out of the TRI when it first opened.

“The concept of the TRI and being in this environment, including its proximity to the hospital, really appealed to me. My interest has always been in translational cancer research. It was the translational environment at TRI that appealed to me and I was very pleased to join the institute,” said Dr Duijf.

“What is really exciting is having so much translational research expertise within the TRI, a lot of people in the same building from different institutions, whether from UQ, QUT, Mater Research or Metro South, and then you have the PA Hospital next door. To have all this is very unique, not just in Australia but also internationally.”

What is genomic instability?

Genomic instability refers to an increased tendency for abnormal changes in the DNA. Genomic instability occurs in cancer cells as they accumulate many genetic and genomic abnormalities, such as mutations and structural or numerical chromosomal changes.

Genomic instability can lead to all kinds of genetic, genomic, transcriptomic and proteomic changes in cancer cells. This can include the abnormal expression of genes, proteins, micro-RNAs and DNA methylation.

About Dr Duijf

Dr Pascal Duijf is a Group Leader and Senior Lecturer in Genetics and Informatics in the School of Biomedical Sciences at the Queensland University of Technology (QUT).

He first became interested in genetics and cell biology in high school. In the final year of high school, his class visited a research laboratory at the local university hospital. The laboratory environment sparked his fascination for biomedical research, especially the concept that by doing research you could potentially manage or treat patients.

Dr Duijf obtained a Bachelor’s degree in Biology and a Master’s degree in Medical Biology from the Radboud University Nijmegen in the Netherlands, before pursuing a PhD degree in Human Genetics at the Radboud University Nijmegen Medical Centre, in the very same laboratory that sparked his interest in research as a high school student. From there, he went on to do his postdoctoral studies at Memorial Sloan-Kettering Cancer Center in New York. His studies there focused on how chromosome instability, the mis-segregation of chromosomes during cell division, contributes to cancer development and progression, with a particular interest in breast and childhood cancers.

In 2013, Dr Duijf established his independent research group at The University of Queensland Diamantina Institute within the TRI in Brisbane, Australia. He took up a position with QUT in 2019. With an interest in breast and other cancers, his group studies genomic instability in laboratory and computational models in order to develop new strategies to improve cancer diagnosis and treatment.

Dr Duijf is an author on more than 60 publications.

Selected recent journal publications

  • Janysek DC, Kim J, Duijf PHG, Dray E. Clinical use and mechanisms of resistance for PARP inhibitors in homologous recombination-deficient cancers. Transl Oncol. (2021) 14(3):101012. doi: 10.1016/j.tranon.2021.101012. PMID: 33516088.
  • Suraweera A, Duijf PHG, Jekimovs C, Schrobback K, Liu C, Adams MN, O'Byrne KJ, Richard DJ. COMMD1, from the repair of DNA double strand breaks, to a novel anti-cancer therapeutic target. Cancers (Basel). (2021) 13(4):830. doi: 10.3390/cancers13040830. PMID: 33669398.
  • Safarzadeh E, Mohammadi A, Mansoori B, Duijf PHG, Hashemzadeh S, Khaze V, Kazemi T, Derakhshani A, Silvestris N, Baradaran B. STAT3 silencing and TLR7/8 pathway activation repolarize and suppress myeloid-derived suppressor cells from breast cancer patients. Front Immunol. (2021) 11:613215. doi: 10.3389/fimmu.2020.613215. PMID: 33679700.
  • Jakobsen MK, Traynor S, Stæhr M, Duijf PG, Nielsen AY, Terp MG, Pedersen CB, Guldberg P, Ditzel HJ, Gjerstorff MF. The cancer/testis antigen gene VCX2 is rarely expressed in malignancies but can be epigenetically activated using DNA methyltransferase and histone deacetylase inhibitors. Front Oncol. (2021) 10:584024. doi: 10.3389/fonc.2020.584024. PMID: 33634013.
  • Tropée R, de la Peña Avalos B, Gough M, Snell C, Duijf PHG, Dray E. The SWI/SNF subunit SMARCD3 regulates cell cycle progression and predicts survival outcome in ER+ breast cancer. Breast Cancer Res Treat. (2021) 185(3):601-614. doi: 10.1007/s10549-020-05997-5. PMID: 33180234.
  • Mansoori B, Silvestris N, Mohammadi A, Khaze V, Baghbani E, Mokhtarzadeh A, Shanehbandi D, Derakhshani A, Duijf PHG, Baradaran B. MiR-34a and miR-200c have an additive tumor-suppressive effect on breast cancer cells and patient prognosis. Genes (Basel). (2021) 12(2):267. doi: 10.3390/genes12020267. PMID: 33673143.
  • Shukla A, Nguyen THM, Moka SB, Ellis JJ, Grady JP, Oey H, Cristino AS, Khanna KK, Kroese DP, Krause L, Dray E, Fink JL, Duijf PHG. Chromosome arm aneuploidies shape tumour evolution and drug response. Nat Commun. (2020) 11(1):449. doi: 10.1038/s41467-020-14286-0. PMID: 31974379.
  • Burgess JT, Bolderson E, Adams MN, Duijf PHG, Zhang SD, Gray SG, Wright G, Richard DJ, O'Byrne KJ. SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer. Sci Rep. (2020) 10(1):18605. doi: 10.1038/s41598-020-75625-1. PMID: 33122723.
  • Suraweera A, Duff A, Adams MN, Jekimovs C, Duijf PHG, Liu C, McTaggart M, Beard S, O'Byrne KJ, Richard DJ. Defining COMMD4 as an anti-cancer therapeutic target and prognostic factor in non-small cell lung cancer. Br J Cancer. (2020) 123(4):591-603. doi: 10.1038/s41416-020-0899-2. PMID: 32439936.
  • Khanna KK, Duijf PHG. Complexities of pharmacogenomic interactions in cancer. Mol Cell Oncol. (2020) 7(3):1735910. doi: 10.1080/23723556.2020.1735910. PMID: 32391427.
  • Brückmann NH, Bennedsen SN, Duijf PHG, Terp MG, Thomassen M, Larsen M, Pedersen CB, Kruse T, Alcaraz N, Ditzel HJ, Gjerstorff MF. A functional genetic screen identifies the Mediator complex as essential for SSX2-induced senescence. Cell Death Dis. (2019) 10(11):841. doi: 10.1038/s41419-019-2068-1. PMID: 31695025.
  • Sinha D, Nag P, Nanayakkara D, Duijf PHG, Burgess A, Raninga P, Smits VAJ, Bain AL, Subramanian G, Wall M, Finnie JW, Kalimutho M, Khanna KK. Cep55 overexpression promotes genomic instability and tumorigenesis in mice. Commun Biol. (2020) 3(1):593. doi: 10.1038/s42003-020-01304-6. PMID: 33087841.
  • Duijf PHG. Low baseline pulmonary levels of cytotoxic lymphocytes as a predisposing risk factor for severe COVID-19. mSystems. (2020) 5(5):e00741-20. doi: 10.1128/mSystems.00741-20. PMID: 32873611.
  • Abdel-Fatah TMA, Ball GR, Thangavelu PU, Reid LE, McCart Reed AE, Saunus JM, Duijf PHG, Simpson PT, Lakhani SR, Pongor L, Gyorffy B, Moseley PM, Green AR, Pockley AG, Caldas C, Ellis IO, Chan SYT. Association of sperm-associated antigen 5 and treatment response in patients with estrogen receptor-positive breast cancer. JAMA Netw Open. (2020) 3(7):e209486. doi: 10.1001/jamanetworkopen.2020.9486. PMID: 32633764.
  • Bhatia S, Monkman J, Blick T, Duijf PH, Nagaraj SH, Thompson EW. Multi-Omics Characterization of the Spontaneous Mesenchymal-Epithelial Transition in the PMC42 Breast Cancer Cell Lines. J Clin Med. (2019) 8(8):1253. doi: 10.3390/jcm8081253. PMID: 31430931.
  • Duijf PHG, Nanayakkara D, Nones K, Srihari S, Kalimutho M, Khanna KK. Mechanisms of genomic instability in breast cancer. Trends Mol Med. (2019) 25(7):595-611. doi: 10.1016/j.molmed.2019.04.004. PMID: 31078431.
  • Kalimutho M, Nones K, Srihari S, Duijf PHG, Waddell N, Khanna KK. Patterns of genomic instability in breast cancer. Trends Pharmacol Sci. (2019) 40(3):198-211. doi: 10.1016/ PMID: 30736983.
  • Emran AA, Marzese DM, Menon DR, Hammerlindl H, Ahmed F, Richtig E, Duijf P, Hoon DS, Schaider H. Commonly integrated epigenetic modifications of differentially expressed genes lead to adaptive resistance in cancer. Epigenomics. (2019) 11(7):732-737. doi: 10.2217/epi-2018-0173. PMID: 31070054.
  • Sinha D, Duijf PHG, Khanna KK. Mitotic slippage: An old tale with a new twist. Cell Cycle. (2019) 18(1):7-15. doi: 10.1080/15384101.2018.1559557. PMID: 30601084.
  • Lin CY, Beattie A, Baradaran B, Dray E, Duijf PHG. Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress. Sci Rep. (2018) 8(1):13904. doi: 10.1038/s41598-018-32272-x. PMID: 30224719.
  • Hosseinahli N, Aghapour M, Duijf PHG, Baradaran B. Treating cancer with microRNA replacement therapy: A literature review. J Cell Physiol. 2018 233(8):5574-5588. doi: 10.1002/jcp.26514. PMID: 29521426.
  • Lin CY, Shukla A, Grady JP, Fink JL, Dray E, Duijf PHG. Translocation breakpoints preferentially occur in euchromatin and acrocentric chromosomes. Cancers (Basel). (2018) 10(1):13. doi: 10.3390/cancers10010013. PMID: 29316705.