Leader cells key to stopping ovarian cancer’s double impact

A diagnosis of ovarian cancer carries a dual threat – the disease itself and the danger of the cancer spreading – now new research has uncovered a crucial factor, leader cells, that is a key to both.

Head of Hudson Institute’s Metastasis Biology and Therapeutics Research Group, Dr Maree Bilandzic, said more than 75 per cent of patients with ovarian cancer present with late-stage disease, often accompanied by extensive metastasis (cancer spreading to other parts of the body), and leader cells are the main culprit.

“We found that keratin-14 (KRT14)-positive leader cells promote tumour progression by suppressing anti-tumour immunity,” Dr Bilandzic said. “By targeting these cells, we aim to develop new therapies to reduce metastasis, enhance immune responses, and improve outcomes for ovarian cancer patients.”

Dr Bilandzic was the first scientist to identify and characterise leader cells in ovarian cancer and thanks to funding from the Ovarian Cancer Research Foundation, she has spent several years working on ways to target those cells.

Her latest research published in Cell Reports, reveals that KRT14-positive leader cells drive ovarian cancer metastasis by suppressing the immune system, and the loss of these leader cells significantly impaired metastasis and helped the immune system better recognise the cancer cells.

“These results are significant because they highlight leader cells as critical drivers of both tumour progression and immune evasion, making them promising therapeutic targets for reducing metastasis and improving immune responses in ovarian cancer treatment.” Dr Bilandzic said.

Target leader cells to stop ovarian cancer

These findings open the way to developing treatments which specifically target leader cells to improve ovarian cancer survival rates, which remain alarmingly low.

Dr Bilandzic said that current treatments are limited by high relapse rates and chemoresistance, but: “Our research addresses this urgent patient need by identifying KRT14-positive leader cells as key drivers of metastasis and immune suppression in ovarian cancer.”

“This is the first study to demonstrate that targeting these leader cells can significantly reduce metastasis and reshape the immune microenvironment, improving the anti-tumour immune response.”

“By uncovering these novel mechanisms and therapeutic targets, this work provides a novel approach to combatting ovarian cancer progression and chemoresistance.”

CEO of the Ovarian Cancer Research Foundation, Robin Penty welcomed the research, saying: “At the OCRF we represent a passionate and committed community who for 25 years have tirelessly fundraised and donated over $25M. This has enabled the OCRF to provide sustained support and a launchpad for ovarian cancer researchers like Dr Bilandzic. By uncovering the drivers of metastasis and recurrence, her work represents crucial progress and hope for the ovarian cancer community.”

Ovarian Cancer Facts

• High Mortality Rate: Ovarian cancer is the most lethal gynaecological cancer, with a 5-year survival rate of only 50% for all subtypes combined, dropping to less than 30% for late-stage diagnoses.
• Late Diagnosis: Over 75% of ovarian cancer cases are diagnosed at advanced stages (Stage III or IV) due to vague symptoms and lack of an effective early detection test.
• Relapse and Resistance: Although most patients respond well to initial treatment, approximately 70% relapse with chemoresistant disease, significantly reducing survival.
• Metastasis-Driven Mortality: The majority of ovarian cancer deaths are due to metastasis, primarily within the peritoneal cavity, highlighting the critical need for treatments targeting metastatic spread.
• Global Burden: In 2022, approximately 324,000 individuals were diagnosed with ovarian cancer globally, and over 200,000 succumbed to the disease, underlining the urgent need for better therapies.
• Highly mobile, invasive ovarian cancer cells called ‘leader cells’ were identified here at Hudson Institute in 2019 as leading the attack on healthy tissue.