Changes in the composition of the extracellular matrix are a key factor in the development and progression of cancers.
A tumour consists not only of a population of cancerous cells, but also a variety of surrounding proteins, secreted factors and cells, collectively known as the tumour microenvironment (TME).
The extracellular matrix (ECM) is a major component of the TME. As well as providing an essential physical scaffolding for the cellular constituents, it regulates crucial biochemical and biomechanical processes involved in tissue morphogenesis and differentiation. The ECM is responsible for modulating tumour cell survival, proliferation, invasion and metastasis as well as angiogenesis, immune response and resistance to treatment.
Deconvoluting the complexity of the tumour ECM landscape and identifying the interactions between the many cell types, soluble factors and extracellular-matrix proteins has proved to be extremely challenging. It is thus crucial to develop and rigorously study preclinical models of ECM in different cancer types to overcome this translational hurdle and move clinically relevant therapies from bench to bedside.
Cancer is the second leading cause of death globally, accounting for approx. 10 million deaths in 2020. Untreatable solid tumours underpin these global death statistics.
deaths globally in 2020
Pancreatic ductal adenocarcinoma (PDAC), develops in the ducts of the pancreas. PDAC is the most common pancreatic malignancy and accounts for 95% of all pancreatic cancers.
PDAC is a highly aggressive malignancy and difficult to treat. Surgical removal of the tumour is the only chance for cure and in 80-90% of cases where the disease presents clinically it is not surgically resectable.
With 460,000 new cases reported in 2018, the global incidence rate of PDAC is 9.5 per 100,000.
Use of 3-D in vitro models based on tissue specific ECM from pancreas or liver enables modelling of primary and metastatic tumours and sensitivity and resistance to drug treatments.
PDAC is always fatal and is the 3rd most common cause of death from cancer in the West. The liver is the common site for metastasis.
most common cause of death
from cancer in the West
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC occurs most often in people with chronic liver diseases, with over 80% of cases derived from liver cirrhosis.
This key association between cirrhotic ECM and HCC development has yet to be fully explored. While treatment options are available, HCC remains the second most common cause of cancer-related deaths.
HCC has a global incidence of 10.1 per 100,000.
Use of 3-D human liver ECM-based in vitro models provides a clinically-relevant environment to interrogate immune cell exclusion and modulation of the immune response.
HCC is the 5th most common cancer and 2nd most frequent cause of cancer-related death globally.
most common cancer
most frequent cause of cancer-related deaths globally
2. Yang, J.D., et al. 2019. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol: 16,;589–604.