New treatments for advanced prostate cancer

QUT’s Dr Lisa Philp is combining her knowledge of hormones and metabolism to develop a new treatment for late stage prostate cancer.

Based at TRI within the Australian Prostate Cancer Research Centre – Queensland (APCRC-Q), Dr Philp leads the Translational Adipokine Research group. Dr Philp is looking at different metabolic hormones and their role in prostate cancer. Her work also extends to developing a treatment for COVID-19 patients who suffer a severe respiratory response.

To mark prostate cancer awareness month, TRI spoke to Dr Philp about her research.

TRI: What are the key projects you’re working on?

LP:   I’m studying endocrinology and metabolism in prostate cancer. In particular, I’m looking at two different hormones we have identified to be involved in men progressing to advanced-state prostate disease and treatment resistance. We want to try and restore these hormones to normal levels to prevent cancer progression because we know those two pathways are highly involved in progression to treatment resistance and that’s what kills men with prostate cancer at the end of the day. At the moment, once tumours become treatment resistant, there’s very little left in terms of treatment options for these men.

More recently, through Advanced Queensland, were studying these hormones in COVID, so that’s a side- shoot, but very relevant.

TRI: You received a US Department of Defense Prostate Cancer Research Program grant, among others, to progress your work in developing a potential new treatment to slow prostate cancer progression.

LP: Yes, the Department of Defence Idea award has given us three years of funding to work with our collaborators and industry partners to sure up our research that is developing a potential therapeutic and bolstering proof to take it forward to clinic.

We’re progressing a drug to restore the level of a hormone secreted from fat, which is altered by androgen deprivation therapy (ADT). Our hope is the drug will extend survival in men with incurable cancer, or that it can be used earlier in prostate cancer to prevent the development of treatment resistance.

TRI: So your treatment could help improve androgen deprivation therapy?

LP: We believe so. ADT is the main form of therapy for men with later stage prostate cancer. We remove the androgens [male sex hormones] to prevent the tumour from growing, but the treatment can lead to offshoot complications in these men.

When we looked at two specific metabolic hormones in patient samples from men undergoing ADT, we found a link between the men’s prognosis and the levels of the hormones. Men who had higher levels of one hormone were more likely to have metastatic disease, and survive less time. The same went for lower levels of the other hormone.

So you have this hormone axis, and while a shift in the levels of these hormones would normally impact metabolic roles, we’ve identified that it’s also driving hallmarks of cancer.

TRI: How far are you away from trialling the treatment in patients?

LP: We’re working with a great industry partner, the best case scenario is that we could end up in clinical trials in the next few years, but it depends on the science and regulatory approvals.

We’ve got all the proof-of-principle behind us that that drug is efficacious in laboratory models. Now, we’re looking at all different types of models of advanced prostate cancer, and seeing where’s the best patient fit. We also need to see what’s the best way to deal with this drug; how’s it having it’s action; if the tumour’s will become resistant to it, what’s causing that; and will we come in with another therapy and co-therapy to get the best affect from our drug? So, it’s really building a case to position our novel therapy in the clinic.

I’m fortunate to have Professor Colleen Nelson [who leads the APCRC-Q team] as she’s been involved in multiple clinical trials, and has the processes in place to get into clinical trials quickly once we have approvals, but first we have to do hard yards in the lab. 

TRI: Can you tell us some more about your COVID-19 research for which you were awarded a 2020 Advance Queensland Industry Research Fellowship (AU$150,000)?

LP:   Many of the people who die from COVID-19 suffer acute respiratory distress syndrome or ARDS. It’s a major symptom of the disease, which causes uncontrolled inflammation of the lungs and airways, and lands people in intensive care.

The drugs we’re developing for prostate cancer could also prevent the massive damaging inflammation of the airways seen in many of the fatal COVID-19 cases. One of the hormones is inflammatory and one is anti-inflammatory, and so we’ll be using novel drugs to modify inflammation, which is the underlying issue in ARDS.

Basically, the body’s own immune response attacks the tissues in the lung in response to infection causing a hyperactive inflammatory response and we’re hoping that these two novel therapies could reduce the inflammation in the lung and prevent ARDS.

We partnering with industry and clinicians and we’re hopeful we can have an approved treatment ready for clinical trials very quickly.

TRI:  What led you to become a scientist?

LP: I went into university being able to whichever degree I wanted. I wasn’t one of these people that came into science wanting to go into medicine. I thought science could be pretty cool and have a lot of useful outcomes to make change. As soon as I got into the lab, then I knew that was what I wanted to do. I thrive on the problem solving and working out how the data fits into the story. The amount of things you can do coming out with your science degree is huge; for me I was lured by the amazing opportunities in medical research.

About Dr Philp

Dr Lisa Philp heads the Translational Adipokine Research group, within the Australian Prostate Cancer Research Centre – Queensland, based at the Translational Research Institute, Brisbane. Dr Philp originates from a metabolic research background with doctoral and undergraduate training in obesity, nutrition and endocrinology at the University of Adelaide, South Australia. Post-PhD, Dr Philp has built a research career studying endocrine-driven prostate cancer, focusing on the intersection between chronic metabolic dysfunction and the androgen axis in prostate cancer. She has a keen interest in the link between the adaptive adipokine and metabolic hormone changes triggered by androgen targeted therapies, and their role in prostate cancer progression. Dr Philp’s current industry-linked research program, funded by the US Department of Defense and Movember, includes the rigorous preclinical development of new therapeutics targeting adipokine signalling, as a novel treatment modality to combat late-stage metastatic prostate cancer and hopefully overcome treatment resistant disease. Recently Dr Philp was also awarded an Advance Queensland Industry Research Fellowship to develop adipokine targeted therapeutics for the treatment of acute respiratory distress syndrome and COVID-19.

Recent papers

• Philp LK, Rockstroh A, Sadowski MC, Taherian Fard A, Lehman M, Tevz G, Libério MS, Bidgood CL, Gunter JH, McPherson S, Bartonicek N, Wade JD, Otvos L, Nelson CC. Leptin antagonism inhibits prostate cancer xenograft growth and progression. Endocr Relat Cancer. 2021 Apr 29;28(5):353-375. doi: 10.1530/ERC-20-0405. PMID: 33794502.
• Philp LK, Rockstroh A, Lehman M, Sadowski MC, Bartonicek N, Wade JD, Otvos L, Nelson CC. Adiponectin receptor activation inhibits prostate cancer xenograft growth. Endocr Relat Cancer. 2020 Dec;27(12):711-729. doi: 10.1530/ERC-20-0297. PMID: 33112829.
• Tousignant KD, Rockstroh A, Taherian Fard A, Lehman ML, Wang C, McPherson SJ, Philp LK, Bartonicek N, Dinger ME, Nelson CC, Sadowski MC. Lipid Uptake Is an Androgen-Enhanced Lipid Supply Pathway Associated with Prostate Cancer Disease Progression and Bone Metastasis. Mol Cancer Res. 2019 May;17(5):1166-1179. doi: 10.1158/1541-7786.MCR-18-1147. Epub 2019 Feb 26. PMID: 30808729.

Photo courtesy QUT.