Current Projects

Rao Gene Regulation and Translational Medicine Laboratory Brain Cancer Research

 
Professor Sudha Rao and her research team are based at the Gene Regulation & Translational Medicine Laboratory at the QIMR Berghofer Medical Research Institute in Brisbane. 
 
Working with world leading clinical researchers in the field of immunoncology, and using state of the art clinical and translational focus, Professor Rao’s Lab has accelerated its work in advancing novel treatments, and non-invasive diagnostics for primary brain cancer and metastatic brain cancer (more than 90% of deaths in cancer patients are due to metastasis; with young people most likely to develop brain metastasis, for which there are currently no treatments).  

Why we need this research

Currently there are very limited options for diagnosis and treatment of primary brain cancer and metastatic brain cancer
The Rao lab has uncovered signatures using a novel Canadian/TGA gold standard digital pathology system and novel AI-based approaches. This profiles tissue and liquid biopsies to predict the characteristics of a patient’s circulating tumour cells (CTCs) and how responsive those CTCs may be to therapeutics. Importantly, this individualised approach can also monitor these aggressive metastatic cells longitudinally over time. This will enable us to track a patient’s cancer recurrence and response so that therapeutic intervention can be adjusted in real time to the patient’s cancer. The lab can also test cultured samples of CTCs with various drugs to determine responsiveness and the most effective ways to treat each patient’s cancer.   

Professor Rao and her team are making rapid advancements in the following important novel areas:

Digital Pathology Diagnostic Platform: Early intervention blood tests to detect brain cancer or brain metastasis

Professor Rao’s Lab has established the world-first liquid biopsy digital pathology platform – a blood test that combines expertise in epigenetics, digital pathology and measuring and characterising cancer cells in the blood. For the first time, they have been able to monitor the ‘“seeders of metastasis”’ (metastatic initiating cells) – the cells that spread cancer. These ‘seeders’ are critical initiators of metastatic brain cancer and may play a role in primary brain cancers such as glioblastomas. Monitoring these ‘seeders’ has not previously been possible. But now, the Rao Lab has identified the precise molecular/protein make-up of these metastatic initiating cells (MITS) and is now working on validating and characterising the molecular and protein make-up of the metastatic cells that are brain specific metastatic initiating cells (bMITS).   

Using novel technology platforms (not available elsewhere in Australia) and a novel digital pathology platform, the Rao Lab has developed a blood test to identify these bMITS that allows monitoring of these ‘seeders’ before they metastasise to the brain. This also has the potential to diagnose brain metastasis or recurrence of primary brain cancer early. This will enable treatment to intervene when the patient has the highest chance of a successful outcome.

Figure 1: Example high resolution digital pathology image of metastatic cancer cells. In green is a novel epigenetic enzyme target identified by the Rao Lab which has been enriched in aggressive, metastatic cancers. The Marker in red (CSV) identifies mesenchymal, metastatic cancer cells.  

Clinical Diagnostics for brain cancer patients – Personalised medicine

It is essential that therapeutics for brain cancers and brain metastasis act rapidly given the quick progress of these cancers, to target the cancer cells causing primary or metastatic brain cancers and to re-invigorate and allow the patient’s own immune system to kill the cancers. The Rao Lab has pioneered methods using novel technologies that allow in-vitro screening of a patient’s specific live cancer cells to determine which drugs the cancer may respond to.

Figure 2: Rao Lab pipeline for drug screening on patient cancer cells from liquid biopsies. CTC = Circulating Tumour Cell, CSC = Cancer Stem Cell.   

This method addresses the key dilemma oncologists face in not knowing what drugs (such as chemotherapy, or immunotherapy) will be effective for the patient, who is already very sick. A test showing if a patient is likely to respond to a specific treatment reduces the time the oncologist may need to find an effective treatment. Early intervention means a higher chance of a positive outcome. Oncologists could provide individual assessments of the correct treatment, and prioritise patients who may respond to specific therapies. 
 
The Rao Lab has identified an epigenetic marker that is a central switch in resistance to many types of therapeutics. Using this marker, the Lab’s novel blood test predicts and tracks, in a non-invasive manner, the patient’s responsiveness to therapeutics. The Rao Lab has successfully used this technology with a small group of patients to guide the use of immunotherapy for Melanoma. 

The Rao Lab will also refine and validate the novel signature for brain metastatic targeted CTCs and primary brain cancer CTCs. This will enable us to further understand the features of CTCs that come from primary brain cancers or migrate to brain metastases.   

Further funding will help establish this blood test as routine, giving many cancer patients personalised medicine options to prolong survival. 

Summary

Professor Rao and her researchers work closely with a team of committed neurologists and oncologists. The Rao Lab’s early intervention approaches are being taken seriously as a matter of urgency. Currently, primary brain cancer patients deal with invasive surgery, chemotherapy and radiotherapy with a high rate of recurrence. Unfortunately, surgery is not always possible and there are minimal to no treatment options available. The Rao lab has made game-changing developments for early intervention by tracking cancer in the blood before it reappears. As a result, these developments provide an important opportunity for the development of targeted drugs that can destroy these aggressive cancer cells before they metastasize. This screening allows for a personalised approach.   
  
With funding, the Rao Lab will work closely with oncologists to accelerate the progress of these blood tests and drug screening platforms. This will enable them to become a routine part of clinical practice for brain cancer patients. Through this early intervention, the patient can be treated with close, non-invasive monitoring before the cancer returns. Additional funds will refine this signature, develop diagnostic tests and therapeutic targeting to allow this work to move from the bench to the clinic.
  
The Rao Lab currently has blanket ethics for patient recruitment at the Canberra Hospital, Royal Brisbane Women’s Hospital (RBWH) and Monash University Hospital, and is working closely with oncologists to identify and recruit patients with a focus on primary and metastatic brain cancers.