A New Approach to Targeting Treatment Resistance in Breast Cancer

Project Description: Cancer stem cells (CSCs) are responsible for the very early development of breast cancer,  and the spread of primary tumours. Professor Kum Kum Khanna (QIMR Berghofer Medical Research Institute) will investigate a new drug that can make CSCs more susceptible to treatment, hence blocking their activity and improving patient outcomes.

Why this work is needed: Cancer stem cells (CSCs) are often resistant to radiotherapy and chemotherapy. This means that they can continue to grow and promote cancer spread, even during active treatment. Eradicating CSCs would improve treatment response in many forms of breast cancer.

Expected outcomes: Prof Khanna and her team have identified a new enzyme (MLK4) which allows CSCs to resist radiotherapy and chemotherapy treatment. In this study, they will block MLK4 with a range of inhibitor drugs, to assess the efficacy of this dual therapy approach to cause tumour regression and prevent recurrence by reducing CSCs levels.

Project details

The factors that inhibit growth and recurrence of breast cancer are not fully understood, and improving our knowledge is critical to unlock better treatment strategies. It is becoming increasingly evident that the spread of primary cancer can be initiated at a very early stage by a small population of unique cancer cells called cancer stem cells (CSCs). Targeting of these CSCs has emerged as a priority area in cancer therapy.

CSCs are resistant to standard chemotherapy and radiotherapy, and hence additional treatments are required. Prof Khanna’s team have identified a new kinase, called MLK4, which protects CSCs against these standard therapies. This study will test the efficacy of a number of MLK4-inhibitor drugs, which should make the CSCs more susceptible to treatment. This will reduce the number of CSCs in the tumour, hence causing cancer regression and a reduced risk of recurrence.

If the results meet expectations, the team anticipates that they will be able to begin testing a dual therapy approach by 2020, with the aim of eradicating CSCs to suppress the spread of cancer and inhibiting the growth of secondary tumours in distant organs.