2025 Research Highlights: Where Discovery Is Headed

Overcoming therapy resistance in prostate cancer

Vincent Giguère

Therapy resistance remains one of the most urgent challenges in prostate cancer, particularly when tumours evolve into the aggressive neuroendocrine subtype. In a study published in Genes & Development, Professor Vincent Giguère and his team uncovered a critical role for the transcription factor ERRγ in restraining this lethal transition.

Using patient samples and genetically engineered mouse models, the researchers showed that ERRγ activity is lost in neuroendocrine prostate cancer, especially in tumours with functional loss of the tumour suppressor PTEN. ERRγ, a regulator of cellular energy metabolism and a close relative of the androgen receptor, acts as a molecular brake on disease progression. Restoring ERRγ expression reversed neuroendocrine differentiation in human prostate cancer cells, directly linking its loss to aggressive disease.

Integrated transcriptomic and metabolomic analyses identified RET and EZH2 as key downstream drivers activated when ERRγ is lost. Combined inhibition of RET and EZH2 produced enhanced anti-tumour activity in pre-clinical models, pointing to a potential therapeutic strategy for patients with few effective treatment options. This discovery reflects a broader program in Professor Giguère’s lab focused on transcriptional and epigenetic mechanisms that drive prostate cancer progression and resistance.

Targeting the metabolic drivers of metastasis

Peter Siegel

Metastasis remains the leading cause of cancer-related death, and Professor Peter Siegel’s lab is uncovering how metabolic adaptations enable tumours to spread to specific organs. Research highlighted by CIHR in 2025 demonstrated that rewiring cancer cell metabolism can limit metastatic potential, opening new avenues for metabolism-based therapies.

Building on discoveries published in 2024, the lab advanced antibody–drug conjugates targeting claudin-2 into pre-clinical development in 2025 for liver-metastatic colorectal cancer—illustrating a direct path from fundamental insight to therapeutic strategy. With new Cancer Research Society funding, the team is now investigating how the protein PDLIM7 regulates autophagy in metastatic triple-negative breast cancer, aiming to block metastatic progression before it takes hold. Together, these studies demonstrate how mechanistic insight is being translated into actionable targets against aggressive disease.

Refining who benefits from immunotherapy in melanoma

Ian Watson

Despite the success of immunotherapy in melanoma, many patients fail to respond. In 2025, Professor Ian Watson’s lab published a key study in Cell Reports showing that loss of the tumour suppressor NF1 disrupts PD-L1 regulation, allowing tumours to escape immune control.

This discovery expands the biological framework for understanding immune evasion in melanoma and suggests that anti-PD-1 therapies may be relevant across a broader range of NF1-mutant cancers. Using integrated genomic, spatial, and molecular approaches, the lab continues to dissect how tumour genetics shape immune visibility. Extending this work nationally, Professor Watson co-leads a MOHCCN-funded pan-Canadian project integrating large-scale cancer genome datasets to identify low-frequency mutations that influence immunotherapy response—bringing precision oncology closer to clinical reality.

Accelerating innovation for rare cancers

Morag Park

In 2025, Professor Morag Park co-led, with Mark Lathrop, the launch of the Jerry Pelletier Initiative: Diagnostic and Therapeutic Innovations for Rare Cancers, a DNA-to-RNA–funded program designed to close critical gaps in diagnosis and treatment for understudied cancers.

The initiative integrates advanced genomic, transcriptomic, single-cell, and spatial profiling with patient-derived models to rapidly identify biomarkers and test candidate therapies. By linking clinic-to-lab-to-clinic pipelines, the program accelerates the translation of molecular insight into patient-relevant strategies. Building on Jerry Pelletier’s foundational contributions to RNA biology, the initiative applies RNA-based and precision oncology approaches to cancers long overlooked by traditional research pipelines.