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Far too many patients are at risk of pancreatic cancer recurrence after surgery. Adile Orhan, MD, PhD student wants to change that. In a study, she is investigating whether administering blood pressure medication before surgery can increase a patient’s chances of getting through a course of pancreatic cancer without relapse. The aim is for the medication to activate the immune system and reduce patient-experienced mental stress.

Orhan is a co-investigator in the study as part of her PhD dissertation at the Center for Surgical Science (CSS), Department of Surgery, Zealand University Hospital in association with Rigshospitalet, the leading Danish research hospital.

As a junior researcher, Orhan has been awarded the Lundbeck Foundation’s Talent Prize 2024 in recognition of her scientific publications, research performance and dedication to optimising medical care for patients with pancreatic cancer, one of the deadliest forms of cancer.

“The Prize is a huge motivator for me. Many years’ hard work preceded this award, and recognition of that is encouraging. But above all, the prize means so much to me because it will help raise awareness of pancreatic cancer and the need for more research into this disease,” says Orhan.

A life-threatening disease with a poor prognosis

Every year, more than 500 men and just as many women in Denmark are diagnosed with cancer of the pancreas, by which time the majority of them have advanced disease. This means that only about a quarter of patients stand to benefit from surgery, and for more than 60 per cent of those who undergo surgery, the cancer comes back within five years. The 5-year survival rate has increased slightly for women, but for both sexes overall it is between 12 and 16 per cent.

Orhan was drawn into this particular field of research as a medical student when she first encountered patients with pancreatic cancer.

“It’s heart-rending to see patients, who have undergone some of the most invasive surgical procedures, followed by the strongest chemotherapy around, come back after 12-24 months or even earlier with a recurrence. I’m motivated every day to do something about that.”

Orhan’s research includes a meta-analysis comparing several independent studies on the immune system in patients with pancreatic cancer.

“This allowed us to demonstrate that a very specific type of immune system T cells in the tumour determine the survival parameters for this group of patients. So that has consequently been a driver for a lot of my ongoing research.”

Study of blood-pressure lowering medication

In the IMPULS pilot trial co-led by Orhan, the aim is to treat patients with the blood-pressure lowering drug propranolol in order to target the tumour’s microenvironment, meaning the conditions inside and surrounding the tumour.

She is particularly interested in the amount of stress hormones and in which and how many of the immune system’s cells are active at the tumour site.

“Both cancer cells and immune cells have receptors for stress hormones, and when they bind to them, the cancer cells can better divide and survive. As a betablocker, propranolol binds to the receptors, and blocks the hormones,” Orhan explains.

By eliminating the effect of the stress hormones, the theory is that the T cells, which influence survival, have better conditions for fighting the cancer cells.

Previous patient-outcome studies have shown that the survival rate of patients with pancreatic cancer improves when they take betablockers. Orhans’ study is the first randomised study of the effect of pre-operative propranolol in patients undergoing surgery for pancreatic cancer.

Regarding the patient’s mental stress, the propranolol lowers the heart rate and thus reduces anxiety symptoms. This in turn limits the release of stress hormones.

“Anxiety is not a general focus in cancer research. But these individuals, contending with life-threatening disease, are in a state of existential crisis. Added to which, it all happens very fast via the national cancer patient pathways. So my hope is that we will be able to relieve some of their distress before surgery, and at the same time reduce the volume of stress hormones.” 

In the study, 10 days before surgery 30 patients are randomly assigned to treatment with either a placebo or propranolol. So far, Orhan has been able to include 10 patients. And recruiting patients is not difficult.

“I was surprised that patients readily agree to take part in the study, especially given that I talk to them about the effect of anxiety symptoms and nervousness. That indicates this is a great concern for them.”

Multi-modal approach matters

Orhan will be completing the study next year, but is planning a similar study for patients with colon cancer, and has ideas for advancing the research even further. She is involved in several studies, including clinical trials in collaboration with both European and Australian investigators.

In one of her studies, she is comparing tumour tissue samples from a small cohort of patients, whose cancer recurred very soon after surgery, with samples from a cohort who still have had no recurrence five years later to determine what the differences might be between them.

“There may be some differences in the tumour tissue that can tell us something about the patients’ risk of recurrence, and which we might be able to identify one day from biomarkers in blood tests,” she explains.

Orhan is also focused on multimodal therapy, that is, a combination of different treatments. And if it is possible to improve post-operative outcomes for patients, it would make sense to offer therapies in combination with, or after, surgery.

“I am convinced that this aggressive disease has to be tackled from multiple angles. If we try to switch off one cancer signal, another signal will likely be switched on. And I believe we can do a lot for the patients pre-operatively.”

One long-term aim is to investigate if early-stage counselling might lower the risk of cancer recurrence.

“I’m convinced that mind-body interaction influences cancer patient outcomes generally, but also that there is an interplay between cancer cells and healthy cells, meaning immune cells, and the whole tumour microenvironment. This is why my hope is that research going forward will also do more to address psychological factors.”