Precision cancer treatment will continue to make progress

Progress continues to be made through world-leading research to identify which treatments will work best for different sub-types of breast cancer.

Cancer Research UK’s cancer blog tells the story of how scientists made an initial discovery that led to a deeper understanding of how many different sub-types of cancer there are by looking at faults in the DNA of nearly 2000 tumours. They worked with laboratories across the world to confirm their findings. Co-lead researcher Professor Carlos Caldas has defined their outcome as a “universal classification of breast cancer”. They plan in future to do more validation work, looking at around 10,000 tumours.

“This is outstanding work that will bring tremendous benefits to women around the world when it is proven and finalised; it is not yet ready for use in clinics and hospitals,” Breast Cancer Aotearoa Coalition committee member Fay Sowerby says.

“It is well on the path to providing a better understanding to enable better targeting of treatments to get the best results for individual women. There is no one size fits all treatment,” Fay says.

Cancer Research UK’s cancer blog says the work is being carried out by a team led by Professor Caldas, based at the Cancer Research UK Cambridge Institute, and Professor Sam Aparicio at the British Columbia Cancer Agency. It is based on their initial breakthrough research in 2012 that identified breast cancer as 10 different diseases. They subsequently identified an 11th sub-type relating to triple negative breast cancer, when it was realised that this was not a single but quite heterogeneous form of the disease.

Having this knowledge means they are now working to create a test for clinicians to use to identify which sub-type of breast cancer each patient has and to identify specific recommendations for treatment and follow-up. The test will be known as PREDICT Plus.

Fay says “Knowing which treatments will work for each individual gives oncologists better knowledge and means that women will not have to go through unnecessary treatments. For instance, it will be easier to determine if chemotherapy is needed or not. If it is needed, then women will know they will benefit from what can be a harsh treatment and for others they will know they can avoid it.” 

In New Zealand SHON, a biomarker identified by AUT Associate Professor Dong Xu Liu and colleagues, has the potential to select the right patients for certain treatments, avoiding giving ineffective treatments to non-responders. This research was published in Cancer Research - click here and more recently in the  British Journal of Cancer 2019. Expression of the SHON protein predicts the risks of response and relapse in breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment.  His lab is now working to understand how SHON drives the progression of breast cancer and to commercialise the SHON biomarker in anti-oestrogen therapy.

Similarly, Dr Francis Hunter, Fellow of the Cancer Society Research Centre at the University of Auckland and his team as reported in the New Zealand Herald, 28 August, 2018 have employed cutting-edge genetic technologies (functional genomics) to understand mechanisms of drug and radiation responses in cancer, allowing treatments to become more precise and personalised.  One of the drugs they focussed on is trastuzumab emtansine (T-DM1 or Kadcyla), for HER2-positive, metastatic breast cancer for patients that have failed prior treatment with trastuzumab. T-DM1 shrinks tumours in only half of patients and the reasons why others are resistant has remained unclear.

They have been using a tool – CRISPR-Cas9 – to identify genes that control (and thus predict) the sensitivity and resistance to T-DM1 in breast cancer. Using DNA-sequencing technology, his team have systematically been screening all 20,000 genes one-by-one to identify which genes were important to controlling how sensitive those cells were to rejecting treatment. Dr Hunter was reported as saying, "We found that about 600 genes - which is about 3 per cent of all human genes, which is a large number - may have some role in causing resistance to the drug." This work continues as they narrow their focus.

Similar work in the UK being led by Dr Mathew Garnett  (click hereof the Welcome Sanger Institute is said to be accelerating discovery of oncology drug targets, which will lead to a leap in a positive direction, as described by Professor Karen Vousden, Cancer Research UK’s Chief Scientist in the Cancer Research UK blog of 10 April 2019  (click here). This work and its large data sets are freely available to scientists around the world.

Fay says “We know that targeted therapies, for example, selectively restrict the growth and spread of cancer cells by blocking the functions of key molecules that are essential to cancer growth, progression, invasion and metastasis. As the examples above show, therapies do not provide a solution for all and only work in sub-populations. It is therefore important to continue to identify novel actionable therapies that target amplified or over expressed molecules in cancer cells and to ensure they have clinical relevance and will ultimately make a difference for patients.”

“If the treatment people receive works for them, they are less likely to relapse. Ultimately this work should save the health system money because treatments will be targeted in the right way. These savings would ideally lead to more medicines being funded by various Governments including New Zealand as patients receive targeted treatment and fewer patients relapse,” Fay says.

Caldas and his team in the UK have published their latest findings in Nature. The researchers’ work is unique in that they are not just looking at the surface of the tumours for cancer cells such as oestrogen receptors and HER2 but are looking to discover what is happening inside the cells which provides more detailed and reliable information. They wanted a more accurate way to distinguish between different breast cancers to provide a better predictor of the risk of future disease.  “Knowing exactly which sub-type of cancer a person has at a more detailed level and tailoring treatment accordingly through more precise approaches, like this, will ultimately change lives,” Fay says.

 

20 June 2019