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Researcher: Professor Chris Lord
Location: The Institute of Cancer Research
Project title: Finding new ways to treat lobular breast cancer
Key area: Treatment
Project cost: £503,987
To achieve our aim that by 2050 everyone who develops breast cancer will live, we need to speed up the translation of research in the lab into new and effective treatments for patients. We’re bringing together leading researchers and top pharmaceutical companies to pool ideas and resources and ultimately stop women dying from breast cancer.
As part of the Breast Cancer Now Catalyst Programme, we have collaborated with leading pharmaceutical company Pfizer to give researchers unprecedented access to a number of Pfizer’s licensed and investigative drugs as well as vital funding for researchers to test these drugs. This allows us to combine the expertise of our researchers with Pfizer’s compounds and deliver new treatments to patients more quickly.
The E-cadherin protein sits on the surface of the cell and is involved in its connections to other cells. Defects in this protein can lead to cancer, in particular tumours that grow in the milk producing lobules of the breast – the second most common site, after the ducts that carry milk to the nipple. Most of these lobular breast cancers are also ER and PR positive, meaning they should benefit from anti-hormone treatment, but sometimes they don’t respond as well as they should. It is therefore vital that we understand why these cancers don’t respond, and develop new treatments to ensure patients are being given the greatest chance of survival.
Defects in the E-cadherin protein are common in lobular cancers, but also in triple negative breast cancer and in secondary breast cancer that has spread to the brain and spinal cord. However, researchers have found that if a cell lacks the function of a protein called ROS1 as well as lacking E-cadherin, the cell is no longer able to keep itself alive. This suggests a novel way to treat cancers with E-cadherin defects, by blocking ROS1.
Professor Chris Lord will be testing this idea by looking at two separate drugs which block ROS1, crizotinib and lorlatinib, to see if these drugs could be potential new treatments for cancers with defects in E-cadherin.
During this project, Professor Lord and his team will be investigating exactly how drugs that block ROS1 cause the cancer cells lacking E-cadherin to die. The team will also be looking at whether using other drugs in combination with crizotinib makes it more effective. Additionally, they team will be testing whether lorlatinib, a new ROS1 blocker drug not yet available, is more effective than crizotinib. All of this work will be carried out using breast cancer cells grown in the lab, and mice that carry breast tumours.
One of Professor Lord’s colleagues, Professor Nicholas Turner, is currently investigating crizotinib in a clinical trial funded by Breast Cancer Now, to test its ability to treat secondary lobular cancer which carries E-cadherin defects. Professor Lord will use the results and samples collected in this study to find ways to predict whether a particular tumour would be sensitive or resistant to crizotinib.
The information gained from this study alongside the results from Professor Turner’s clinical trial of crizotinib will be used to set up new clinical trials in the near future investigating lorlatinib and other combinations of drugs, which could potentially lead to brand new treatments for breast cancer. For hard to treat cancers that become resistant to treatment, new drugs or combinations of drugs like these are greatly needed so that we can continue giving patients the best chance of survival.
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* Pfizer has provided funding and Pfizer compounds for this research study as an Independent Medical Research grant as part of the Breast Cancer Now Catalyst Programme. Pfizer has no other involvement in this research study.