Defining new targets in liver cancer

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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

*This data represents hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Liver cancer remains on the rise

For decades, the number of liver cancer cases globally have continued to rise.14 In 2020, liver cancer was the third most common cause of all cancer-related deaths.15* Hepatocellular carcinoma (HCC) is the most common form of liver cancer among adults, representing about 75% of all primary liver cancer 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.20-22 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

Treating HCC

Screening for HCC is challenging.25 While early detection is the goal, 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

HCC is staged according to the Barcelona Clinic Liver Cancer (BCLC) system, with the disease stage determining what options are available to patients:26

Treatment for early stage (Stage 0 to A) disease and intermediate stage (Stage B) disease may involve:27,28

  • Surgery to remove the tumour.

  • Liver transplant may be a curative treatment for some patients with early stages of disease.

  • Thermal ablation (also referred to as radiofrequency ablation or microwave therapy) uses heat to destroy cancer cells in patients in the earliest stages of disease.

  • Transarterial chemoembolisation, or TACE is used to treat early- and intermediate-stage tumours that cannot be treated with surgery or thermal ablation. During the procedure, physicians deliver chemotherapy directly into the artery, which is then blocked to increase the tumour’s exposure to the medication.

Treatment for intermediate stage (Stage B) and advanced stage (Stage C) disease may involve:29

  • Systemic therapy is used in Stage B patients who are ineligible for other treatments or progressed on other therapies, as well as Stage C patients. There is a critical unmet medical need for new treatments that can treat patients with advanced stages of HCC. Ongoing research has revealed Immuno-Oncology therapies show promise in this challenging setting.

Our approach

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.30

Treatment that reverses immunosuppression is called immunotherapy, and there are now multiple immunotherapies that may lead to anti-tumour activity.30,31 Our goal is to explore immunotherapy combinations for overcoming the drivers of immunosuppression involved in liver cancer, and with the aim of transforming survival for patients with liver cancer.

These efforts continue to build on the practice-changing results of our diverse, Immuno-Oncology clinical programme in multiple, solid tumours, and we remain committed to harnessing the versatile power of immunotherapy and immunotherapy combinations to redefine cancer care.

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Veeva ID: Z4-42953
Date of prep: May 2022