Defining new targets in liver cancer
The liver performs numerous vital functions including filtering the body’s blood supply and – as a key organ of the immune and circulatory systems – contains numerous immune cells that defend the body against blood-borne pathogens and aid in wound healing.1,2,3,4 In addition, the liver is regenerative, meaning it can replace damaged tissue by regrowing its existing tissue – up to two-thirds of its total size.5,6,7 The unique pathogen-clearing and wound-healing properties of the liver require that resident immune cells are often active and ready to protect the body from harm.3,4 As part of this ability to protect the body, liver immune cells are typically also able to detect cells that have become abnormal, attacking and removing them before they can divide and grow into dangerous tumours.3,8 This state of immune readiness is a critical way liver immune cells are able to rapidly respond to pathogens and injury.9
Chronic inflammation – the “Achilles’ heel” of the liver
Inflammation is a natural part of the immune system’s standard reaction to threats.9 Ordinarily, inflammation is acute, or short term, and ends once a pathogen is removed or an injury is healed.9 But there are cases when the inflammatory response persists.10 Liver damage from hepatitis virus infection or as a result of excessive and prolonged alcohol intake can lead to chronic inflammation that ultimately may interfere with the typical ability of liver immune cells to attack and remove abnormal cells.10,11 When immune cells are hampered in this way, we call it immunosuppression.12 Unfortunately, immunosuppression in the liver can last even after the damaging period.5 With immune cells less able to attack and remove abnormal cells, cells in the liver are more likely to grow into cancer.11 Removing immunosuppression and restoring the ability of immune cells to attack and remove abnormal cells may be a key way to manage cancers that arise in the liver. 11,13
Liver cancer remains on the rise
For decades, the number of liver cancer cases globally have continued to rise.14 Liver cancer is the the sixth most commonly diagnosed cancer worldwide.15 However, due to poor outcomes, it is the third leading cause of cancer death.15 Hepatocellular carcinoma (HCC) is the most common type of liver cancer, representing about 80% of all cases.16,17
Why is liver cancer so prevalent?
Between 80 and 90% of HCC cases develop as a result of cirrhosis, the most common of which is infection with hepatitis B or C viruses.17 These viruses are widespread and challenging to manage, particularly in many developing parts of the world, making reducing the global burden of HCC difficult.18,19 More than 72% of the world’s HCC cases are found in Asia where these viruses are endemic.20,21,22 China alone accounts for more than half of all newly diagnosed liver cancer cases and deaths, despite containing less than 20% of the world’s population.23
Ongoing programs focused on prevention and screening of hepatitis are important to reduce the number of new HCC cases.17,18,19 However, there remains an urgent need for research that will provide more effective treatment options for patients with HCC than what is available today.24
Screening for HCC is challenging.25 Most signs and symptoms appear when HCC is at an advanced stage, and early-stage tumours are often difficult to detect in a physical exam.25 As such, most patients are diagnosed at later stages of the disease when treatment options are limited.25
Other standard treatments may involve
Using heat or alcohol to destroy cancer cells – known as tumour ablation.26
Replacing the liver with a donor liver – a treatment option limited by the availability of donors, long wait times, and the risks associated with transplantation.26
Delivering chemotherapy directly to the cancer cells via an artery – known as transarterial chemoembolisation, or TACE.26
Blocking cell pathways that lead to cancer cell growth – using targeted drug therapies such as multi-kinase inhibitors.26
Implanting radioactive beads into the tumour to destroy cancer cells – known as transarterial radioembolisation, or TARE.27
Pioneering new research has deepened our understanding of the processes leading to the immunosuppression involved in liver cancer.13 Mounting evidence has shown that reversing immunosuppression may restore the ability of immune cells to attack and remove cancer cells, potentially slowing growth of or shrinking tumours.28 Treatment that reverses immunosuppression is called immunotherapy, and there are now multiple immunotherapies that may lead to anti-tumour activity.28,29 Our goal is to explore immunotherapy combinations for overcoming the drivers of immunosuppression involved in liver cancer, and with the aim of improving survival for liver cancer patients.
These efforts continue to build on the practice-changing results of our broad, Immuno-Oncology clinical programme in multiple, solid tumours, and we remain committed to bringing the versatile power of immunotherapy and immunotherapy combinations to as many patients as may benefit.
More about liver cancer
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Document ID: Z4-22319
Date of prep: May 2020