Wu Lab - Cancer therapeutics

The ultimate goal of my research is to develop effective strategies for detection and treatment of ovarian and breast cancers, and translate these research findings into the clinic. Specifically, we are interested in (1) Developing strategies to overcome immunosuppression in ovarian and breast cancers; (2) Developing biomimetic nanoparticle platforms for tumour-targeted delivery of RNAi therapeutics; and (3) Understanding the role of exosomes in ovarian cancer progression.

Harnessing the immune system to battle ovarian cancer

Ovarian cancer is the most lethal form of gynaecologic malignancy with 5-year survival rate of only 35-40%. The high recurrence rate presents a major challenge in the clinical management of high grade serous ovarian cancer. While stimulating our own immune system to recognize and attack tumour cells represents an attractive means to facilitate complete elimination of tumours, emerging data suggest that many of the immunotherapy tools have promising but limited effects in ovarian cancer. To address this unmet need, my lab focuses on developing novel strategies to enhance anti-tumour immunity in ovarian cancer. We utilise systems-based approach combined with RNA interference technology to target clinically important immune suppressive factors with the goal of enhancing cytotoxic T-cell functions in ovarian tumours. Ultimately, the ability to effectively stimulate the immune system to attack tumour cells could significantly improve outcomes of women with ovarian cancer. The technology we develop can also be applied for treatment of other cancer types.

Tumour-targeted delivery systems

My lab is focusing on developing clinically translatable tumour-targeted delivery systems for RNAi therapeutics. SiRNA, a short double stranded RNA, represents an attractive means to mediate down-regulation of target genes. Unlike conventional small molecule inhibitors or monoclonal antibodies, siRNA is highly specific to its target and has a much wider clinical applicability as its use is not limited to targeting ligands or kinases. Several early phase trials have reported clinical responses in cancer patients after RNAi therapy. Despite the promise of existing synthetic delivery systems, the reported spleen, liver, and immune-related toxicities in early phase clinical trials must be overcome before RNAi can meet the standards for clinical use. To address this need, we are developing a novel and biocompatible delivery strategy using naturally occurring exosomes that are highly efficient in delivering their cargo to recipient cells. Being natural transporters, exosomes are also less likely to exert toxicity or elicit immune responses.

Role of exosomes in cancer progression

Exosomes are tiny lipid vesicles that can be generated by many cell types in our body. They serve as effective means for cells to communicate with each other, even when they are located remote from each other. Cancer cells, in particular, produce large quantities of exosomes with distinct markers and characteristics. The content of these exosomes highly reflects the characteristics of the cells that generate them. Our lab is interested in understanding the role of exosomes in cancer progression and metastasis.