Unravelling the function of a novel therapeutic target in the tumour microenvironment to prevent breast cancer and metastasis

Suitable for PhD, Masters or Honours Students

BACKGROUND

Metastasis, the spread of cancer cells from the primary tumour to surrounding tissues and distant organs, is the major cause (90%) of cancer mortality. Current cancer treatments mostly focus on targeting primary tumours, as the treatment or prevention of metastasis continues to have limited success. The complexity of the tumour-microenvironment (TME) and factors contributing to metastasis are not fully understood; therefore, improving our knowledge is critical for developing better treatment strategies. There is also an unmet need to improve the efficacy of current treatments such as immunotherapies and targeted therapies for metastasis to improve the overall survival of patients. We have identified a cancer-specific protein, which is highly expressed in a wide variety of cancers, its expression correlates positively with metastatic potential and worse patient outcomes. The inhibition of this target can hinder tumourigenesis, and increase survival in patients. Metastasis is regulated by a complex interplay with noncancerous cells (stroma) within the TME. These interactions are regulated at various levels, including direct cell–cell communication and tumour infiltration by immune cell components, binding of extracellular matrix components and secreted factors such as cytokines (immune modulators), and exosomes (type of extracellular vesicles) which are mediators of signalling and cellular communications in TME. How these complex processes happen, is the focus of this project.

AIM

1) Underpinning the functional role of a specific gene in TME and metastasis to identify molecular mechanisms of immunoregulation and signalling pathways.

2) Exploring the biological role of a specific gene in extracellular matrix remodelling, cytoskeletal rearrangements, migration and signalling events.

SIGNIFICANCE

Specifically, we are investigating mouse models of cancer to develop new approaches which exploit the dynamic nature of TME. Professor Khanna’s laboratory has generated many tools including but not limited to: genetically engineered mouse models (GEMMs), tumour xenograft models, and cell lines with the constitutive or inducible potential of gene knockdown. These tools can be used for the phenotypic, biochemical and cellular analysis of TME, tumour initiation, progression and metastasis.

TASKS

This project will apply a wide range of techniques in cell biology and tumour immunology to understand how cancer cells interact with TME and the student will become familiar with these techniques and possibly be involved in the publication depending on the achieved results.