Blocking cancer cells' in-built survival mechanisms could slow tumour growth and make existing treatments more effective, according to a new University of Sheffield study
While the dense, scar-like wall around aggressive breast and pancreatic tumours restricts their normal nutrient supply, the cells adapt by using collagen as a backup fuel, revealing a crucial vulnerability scientists can exploit to starve the cancer
Disabling this survival mechanism could make standard cancer treatments like chemotherapy much more effective, allowing doctors to use lower doses that cause fewer severe side effects
Targeting how cancer cells adapt and survive in nutrient-deprived environments could slow tumour growth and make existing treatments more effective, according to new University of Sheffield research.
Focusing on aggressive breast and pancreatic cancers, scientists have discovered how tumours surrounded by a protective 'scaffold' of dense, scar-like tissue manage to thrive - despite this scaffold severely restricting the blood supply and nutrient delivery essential for growth.
Researchers from the Sheffield Centre for Cancer Research discovered that the key lies in a protein abundant throughout the human body: type I collagen. The Cancer Research UK-funded study reveals that type I collagen, a major building block of the scaffolding around tumours, helps cancer cells adapt to these challenging, nutrient-lacking conditions.
In tumours like breast and pancreatic cancer, up to 90 per cent of the mass consists of this scaffolding, known as the extracellular matrix. Typically, if you starve cancer cells of glucose - the primary source of energy for cells in the body - they die. But when this scaffold is present, the cells adapt by finding another fuel source.
When glucose levels drop, collagen triggers signals that allow cancer cells to switch fuel sources and absorb essential amino acids: the building blocks needed for their growth and survival. This process relies on a transporter protein called LAT1, which acts like an internal delivery system to pull amino acids into the cancer cells.
Laboratory tests on cellular models showed that blocking LAT1 transporters and interrupting the cell's interaction with collagen starves the cancer cells of vital nutrients, offering a promising target for future therapies.
Lead author Dr Elena Rainero, a Senior Lecturer at the University of Sheffield, said: "Because cancer cells adapt so quickly, single treatments rarely eradicate a tumour entirely.
"But if we can block this collagen-driven survival mechanism, we could slow the growth and spread of cancer cells while making them more sensitive to existing treatments like chemotherapy.
"That could allow clinicians to lower treatment doses, reducing severe, debilitating side effects for patients while making the therapies more effective."
Ultimately, the Sheffield discovery could enable lower, less toxic chemotherapy doses while making treatments significantly more effective at starving aggressive tumours and stopping them from spreading and taking root elsewhere.
Read the study in full, published in the PLOS Biology journal, here.
