Written by:
Global Franchise Head, Immuno-Oncology & GI Cancers, AstraZeneca
Global Clinical Strategy Head, GI Oncology, AstraZeneca
Patients living with gastrointestinal cancers urgently need new treatment options as prevalence and mortality rates are steadily on the rise. That’s why we are pushing the boundaries of science through clinical innovation to deliver more treatment options to patients. Through these next-generation modalities, our goal is to one day eliminate GI cancer as a cause of death.
At AstraZeneca, our ambition is to one day eliminate cancer as a cause of death. In gastrointestinal (GI) cancers, we’re working to deliver on this ambition by improving standards of care and advancing transformative technologies.
The Growing Global Burden of GI Cancers
While tremendous progress has been made in the treatment of many types of GI cancers, they are collectively the fifth leading cause of cancer-related deaths globally.1 In 2022, approximately 5 million people were diagnosed with a GI cancer, including gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers, worldwide – more than lung and breast cancer combined.2 While the global overall cancer mortality rate has been slowly decreasing, the rate of GI cancer deaths is predicted to increase.3-4 By 2040, it’s estimated there will be 7.5 million new cases and 5.6 million deaths from a GI cancer.3 This trend is particularly concerning given the rising incidence of certain GI cancers in younger people under 50 years of age.5-6
Patients with GI cancer also face high recurrence rates and a poor prognosis.7 New approaches are needed to improve patient outcomes, particularly in earlier disease stages where there is the greatest potential for survival.
Changing Standards of Care in GI Cancers
We're investigating a broad range of scientific approaches to target GI cancers, with a clinical strategy that aims to address the following areas: antibody-drug conjugates (ADCs), DNA Damage Response (DDR) therapies and immunotherapies.
Our clinical strategy for GI cancers aims to address the following areas of focus:
- Advancing potential treatment combinations to drive deeper, more durable responses and overcome treatment resistance.
- Exploring new approaches in earlier, curative-intent stages of disease where novel therapies may offer the greatest opportunity to impact patients’ lives.
- Developing personalised approaches by pursuing novel biomarker-driven therapies.
Advancing Transformative Technologies
AstraZeneca is committed to a world without GI cancers. We’re investigating next-generation treatment modalities, including ADCs, bispecific immunotherapies, cell therapies and T-cell engagers (TCEs), as we strive to improve outcomes for patients.
ADCs
We’re advancing mechanisms that harness an antibody’s tumour-targeting ability to deliver chemotherapy directly into cancer cells. ADCs provide a more selective way to kill these cells than conventional chemotherapy, while minimising damage to healthy cells.8 These medicines consist of an antibody – which binds to a target protein on the surface of cancer cells – attached via a chemical linker to a powerful chemotherapy payload.8-9 After binding to its target, the ADC is internalised by the cancer cell where it releases the cytotoxic payload.9
We’re investigating ADCs targeting emerging proteins such as CLDN18.2, both as monotherapy and in combination with other treatment approaches, in gastrointestinal cancers.
Bispecific Immunotherapies
Bispecific immunotherapies are engineered to bind to two different targets – for example, two immune checkpoints – to help induce an immune response against cancer.10-11 The hypothesis is that this multi-targeting approach may enhance the antitumour immune response while potentially minimising systemic toxicity.12 Our PD-1/TIGIT and PD-1/CTLA-4 bispecific immune checkpoint inhibitors are being investigated for the potential treatment of multiple forms of GI cancers.
Cell Therapies and TCEs
Our next-generation immunotherapies also include cell therapies and TCEs.
Cell therapies involve infusion of immune cells either from the patient’s own body (autologous) or from a healthy donor (allogeneic).13 Certain cells have been modified in a laboratory to create a “living medicine” that can recognise and attack their specific cancer cells.14 Cell therapies called chimeric antigen receptor T-cells (CAR-Ts) have shown meaningful benefit for some patients with blood cancer; however, it has been challenging to extend this success to solid tumours like GI cancers, where the tumour microenvironment poses physical and immunological barriers.15 We’re researching next-generation approaches as we strive to address these barriers and develop innovative treatments for patients, including CAR-Ts targeting cell surface proteins like Claudin 18.2 and Glypican 3 (GPC3) that are highly expressed in certain GI cancer cells.16-17
T-cell engagers are antibodies designed to recognise and bind to two or more antigens simultaneously, and are engineered to redirect the immune system’s T-cells to recognise and kill cancer cells.18 They are thought to work by binding to a target on the surface of a cancer cell and to targets on T-cells, thereby bringing them into close proximity and activating the T-cell to attack the cancer.19 We’re investigating the potential of a TCE bispecific antibody targeting both Claudin 18.2 and CD3, a protein found on T-cells.
Our ambition to one day eliminate cancer as a cause of death is a bold vision. It’s one that we’re committed to realising by pushing the boundaries of science, with the goal of discovering treatments that have the potential to one day revolutionise GI cancer care.
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