Genome a treasure trove for new disease treatments and diagnostics

Queensland scientist Dr Mark Adams is uncovering potential new treatment targets and diagnostics for a range of diseases, including lung, breast, colorectal and endometrial cancers and SARS-CoV-2 (COVID-19) as he delves into the human genome.

Based at the Translational Research Institute (TRI) with the Queensland University of Technology (QUT) Cancer and Ageing Research Program (CARP), Dr Adams is studying the interplay of molecules that control cell cycle, cellular growth and maintenance of genomic stability to identify molecules, which hold potential as predictive biomarkers or targets for future therapeutics.

Dr Adams says all his research has a translational focus, driven by a desire to improve patient outcomes. When it comes to cancer, he is investigating several possible genes.

“Our lead candidate is a diagnostic biomarker for non-small cell lung cancer patients who are resistant to standard chemotherapy treatment,” says Dr Adams.

“We’re in the preclinical testing stage, but I’m working to secure further grants and industry funding to progress this research into clinical trials in combination with a new candidate therapeutic.” 

New lung cancer diagnostic and treatment combo

Dr Adams began his journey towards improved treatments for lung patients during his postdoctoral fellowship, which he began almost a decade ago. At the time, he started working with a panel of possible biomarkers for cancer and aging.

“From an initial screening process involving hundreds of genes, we’ve been able to isolate five to six promising diagnostic biomarkers and it’s just exploded from there,"says Dr Adams.

“We’ve just submitted a provisional patent application for our most prominent candidate. We’re looking at this particular marker in non-small cell lung cancer, but it’s also present in breast and colorectal cancers so it could have a much broader impact."

If shown to be accurate within a clinical setting, the diagnostic could potentially change the way people with non-small cell lung cancer are treated. Non-small cell lung cancer accounts for around 85% of all lung cancers, with the majority of patients presenting with advanced stage disease.

According to Dr Adams, chemotherapy remains a common clinical treatment option for this cancer, but only a minority of patients respond due to drug resistance, which impairs chemotherapy effectiveness.

“If we can select out the people with lung cancer who won’t benefit from chemotherapy and offer them other treatments, we can potentially increase their survival rate as well as reduce their exposure to toxicity from treatment which isn’t beneficial. We need to do further pre-clinical studies before we move into patient trials, but we’re optimistic that the new diagnostic, in combination with a possible new therapeutic we’ve found, will benefit a large number of lung cancer patients,” says Dr Adams.

The next step in Dr Adams work is to examine large numbers of patient samples and their treatment records to see if his diagnostic is accurate in the clinical setting. If it is, he hopes to move to a trial in patients using both the diagnostic and the new treatment within the next five years.

Genomic instability

The discovery process for Dr Adams’ research is driven by the study of the cell cycle and cell growth and how these processes interface with the prevention of genomic frailty. These cellular processes are tightly regulated and controlled by a variety of molecules, but these processes can be manipulated in diseases such as cancer, according to Dr Adams.

“For example, the DNA repair capacity of human cells declines with age, in a process that is not clearly understood,” he says.

“Trying to understand these processes and how they are involved in disease underlies all of our work. It’s how we find disease biomarkers.

“One way we do this is by treating different cells with chemotherapies to see how genes respond. From this, we are able to identify important genes. We try to understand what these genes are doing and why, to see if we can exploit them for diagnostics or targets for treatments.

“This is basic research, but it's also very translational. We want to exploit the cellular processes to improve patient treatment.”

A novel treatment for people with COVID-19

Dr Adams received a 2020 Advance Queensland COVID-29 Industry Fellowship for research into stopping COVID-19 by targeting viral replication. He is investigating the effectiveness of a novel anti-cancer therapeutic candidate as an inhibitor of SARS-CoV-2. The research looks at using therapeutic treatment to switch off the virus's ability to replicate, and reduce severity of COVID-19 symptoms. His partners in the project include The Princess Alexandra Hospital and CARP Pharmaceuticals.

About Dr Mark Adams PhD

Brisbane born and raised, Dr Adams completed his undergraduate studies at the Queensland University of Technology (QUT) before undertaking a PhD at the Mater Research – University of Queensland. Following his PhD, he received an NHMRC Fellowship to undertake postdoctoral work at QUT. Dr Adams now leads a team within the QUT Cancer and Ageing Research Program, based at the Translational Research Institute. His team has funding from the NHMRC, the International Lung Cancer Foundation and Cure Cancer Australia. Overarching all Dr Adams’ projects is an interest in cell cycle control and maintenance of genome stability, and how deregulation of these mechanisms contributes to cancer and disease. As to why he chose a career in science, he puts it down to an insatiable curiosity about how things work in the body and a desire to understand what is going on.

Research projects

Please contact Dr Adams for available research projects via email: [email protected].

Recent journal publications

• Suraweera A, Duff A, Adams MN, Jekimovs C, Duijf PHG, Liu C, McTaggart M, Beard S, Byrne KJO, Richard DJ., “Defining COMMD4 as an anti-cancer therapeutic target and prognostic factor in non-small cell lung cancer.” Br J Cancer, 2020 May 22. doi: 10.1038/s41416-020-0899-2.

• He Y, Davies CM, Harrington BS, Hellmers L, Sheng Y, Broomfield A, McGann T, Bastick K, Zhong L, Wu A, Maresh G, McChesney S, Yau Wong K, Adams MN, Sullivan RC, Palmer JS, Burke LJ, Ewing AD, Zhang X, Margolin D, Li L, Lourie R, Matsika A, Srinivasan B, McGuckin MA, Lumley JW, Hooper JD., “CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of β-catenin and E-cadherin.”, Oncogene,  2020 Jan;39(1):219-233. doi: 10.1038/s41388-019-0983-3. Epub 2019 Aug 30.

• Bolderson E, Burgess JT, Li J, Gandhi NS, Boucher D, Croft LV, Beard S, Plowman JJ, Suraweera A, Adams MN, Naqi A, Zhang SD, Sinclair DA, O'Byrne KJ, Richard DJ., “Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage.,” Nat Commun., 2019 Dec 3;10(1):5501. doi: 10.1038/s41467-019-13167-5.

• Ryan SL, Beard S, Barr MP, Umezawa K, Heavey S, Godwin P, Gray SG, Cormican D, Finn SP, Gately KA, Davies AM, Thompson EW, Richard DJ, O'Byrne KJ, Adams MN, Baird AM, “Targeting NF-κB-mediated inflammatory pathways in cisplatin-resistant NSCLC.”, Lung Cancer, 2019 Sep;135:217-227. doi: 10.1016/j.lungcan.2019.07.006.

• Croft LV, Bolderson E, Adams MN, El-Kamand S, Kariawasam R, Cubeddu L, Gamsjaeger R, Richard DJ, “Human single-stranded DNA binding protein 1 (hSSB1, OBFC2B), a critical component of the DNA damage response.”, Semin Cell Dev Biol., 2019 Feb;86:121-128. doi: 10.1016/j.semcdb.2018.03.014.

• Adams MN, Burgess JT, He Y, Gately K, Snell C, Zhang SD, Hooper JD, Richard DJ, O'Byrne KJ., “Expression of CDCA3 Is a Prognostic Biomarker and Potential Therapeutic Target in Non-Small Cell Lung Cancer.”, J Thorac Oncol., 2017 Jul;12(7):1071-1084. doi: 10.1016/j.jtho.2017.04.018.