Breast cancer is the most common cancer diagnosed in women with many patients progressing to advanced stages where prognosis and morbidity is poor. Ninety percent of patients will succumb to their disease primarily due to metastasis. Metastatic cancer cells are invasive, migratory and highly resistant to standard chemotherapies. Therefore, greater knowledge is needed to characterise mechanisms by which cancer cells become resistant to anti-cancer agents. A mechanism by which cancer cells may develop resistance is through stimulating stress response pathways, in particular, the heat shock response (HSR). This pathway is regulated by heat shock factor-1 (HSF-1), which initiates the transcription of heat shock proteins (HSPs) alongside many non-HSPs. HSPs protects normal cells during exposure to proteotoxic stress. However, in cancer, HSF-1 has been found to facilitate pro-metastatic pathways, separate from the typical HSR. Additionally, HSF-1 protein expression is significantly increased in multiple cancers and correlates with poor clinical outcomes, however, little is known regarding the role of HSF-1 in the resistance/sensitivity of cancer cells to current therapeutics. This project aims to examine whether HSF-1 plays a direct role in mediating chemotherapeutic resistance in cancer cells and identify whether inhibiting HSF-1 action can enhance the sensitivity of cancer cells to anti-cancer therapeutics. To assess chemotherapeutic stress within the cancer cells we have generated a reporter assay that expresses bioluminescent upon transcription of the Heat Shock Element, indicative of HSF-1 activity, and screened drugs that are currently applied in the clinic or are in clinical trials. We then transfected breast cancer cell lines having different metastatic propensity with an inducible-HSF-1 knockdown construct, treatment of these cells with the drugs that we found to induce HSF-1 activity will allow us to observe changes to the sensitivity of these cancer cells to drug efficacy. Ultimately, this knowledge will help to identify and improve therapeutic management leading to better outcomes in metastatic cancers.