Pancreatic cancer: How it starts spreading and how to stop it

pancreatic cancer, cancer diagnosis, world cancer day
Only a small percentage of the patients survive pancreatic cancer.
Photo credit: SHUTERSTOCK

What you need to know:

  • Pancreatic cancer is highly resistant to treatment with nearly all patients experiencing recurrence or metastasis.
  • This has seen oncology researchers dig deeper in a bid to gain treatment and management control over the disease.

Pancreatic cancer is ranked as one of the most lethal cancers to treat or survive.  It’s highly resistant to treatment with nearly all patients experiencing recurrence or metastasis. This has seen oncology researchers dig deeper in a bid to gain treatment and management control over the disease.

One of the latest efforts is a research by the University of California. The analysis has found out that stress-tolerant cells drive tumour initiation in pancreatic cancer and contribute to the disease’s high resistance to chemotherapy and its propensity for metastasis.

Recruit cells

Pancreatic tumour-initiating cells launch their assault by creating their own tumour-promoting microenvironment. They then utilise this environment to recruit surrounding cells into their network. With this finding, oncology researchers from the University of California (UC) have recommended that treatment methods can start limiting the progression, relapse and spread of pancreatic cancer by targeting this initiation pathway.

According to Dr David Cheresh, vice-chairman of the Department of Pathology at the UC San Diego School of Medicine, cancer cells experience a loss of adhesion to other cells and the extracellular matrix – the web of macromolecules that encase and support all cells – in the early stages of tumour formation.

“This isolation leads to a local lack of oxygen and nutrients. Most cells do not survive such isolation stress, but a certain group of cells can,” said Dr Cheresh, who was the lead researcher in the study. 

He explained that tumour-initiating cells usually play a major role in the formation, recurrence and metastatic spread of tumours and have adequate resilience to early substandard conditions. "Stress-tolerant tumour-initiating cells have reduced levels of a tumour-suppressive microRNA (miR-139-5p). This leads to the up-regulation of lysophosphatidic acid receptor 4 (LPAR4), which is a G-protein-coupled receptor on the cell surface,” said Dr Cheresh.

“Lysophosphatidic acid receptor 4 is not normally found on happy cells, but it gets turned on in stressful environments to help the cells survive, which is particularly advantageous for tumour-initiating cells.” 

The researchers further established that the LPAR4 expression promotes the production of new extracellular matrix proteins. This production allows the solitary cancer cells to start building their own tumour-supporting microenvironment.

"Our findings have established a critical role for LPAR4 in pancreatic tumour initiation, and a likely role in other epithelial cancers such as lung cancer," said Dr Cheresh. 

"It is central to tumour-initiating cells' ability to overcome isolation stress and build their own niche in which tumours can form."Dr Cheresh recommended that the most effective way of combating pancreatic cancer is by targeting the LPAR4 pathway or disrupting the fibronectin – integrin interaction. A new drug targeting this pathway could be used as a prophylactic in patients at high risk of developing the disease. It could also be utilised to prevent new tumours from forming in cancer cases with a high likelihood of metastasis. 

According to figures from Our World Data, a research team based at University of Oxford, 667 patients died from pancreatic cancer in Kenya in 2017 in comparison to 188 in 1990. The figures also showed that pancreatic cancer accounts for one per cent of cancer cases in Kenya. However, the rise in the number of patients who succumbed to the disease over the period under review was qualified as the fastest- rising killer cancer in Kenya and the East African region, where the disease claimed 36,000 lives over the past 27 years between 1990 and 2017. Globally, pancreatic cancer has the lowest survival rate among all common cancers. Only seven per cent of patients survive up to five years after diagnosis.


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