Bioengineered Enzyme-Scissors Uncover New Pathways For Tackling Cancer Resistance

10 Aug, 2023: Scientists at Stanford University have developed a biomolecule that targets and eliminates mucins exclusively within cancer cells. This finding holds great promise for potential cancer treatments in the future.

Mucins are protein molecules covered in sugar molecules, serving as a main line of defence against physical harm and dangerous microorganisms in the body. However, cancer cells can hijack these mucins to support their own survival. Removing mucins from cancer cells presents a potential treatment strategy, yet this approach must be carefully considered since mucins come in different types across all mammalian cells. Indiscriminate mucin targeting might lead to unexpected consequences.

The Stanford-led research team has developed a solution that involves creating an enzyme-based tool akin to scissors. This tool consists of a protein-cutting enzyme called mucinase, which is capable of precisely cutting mucins, along with a cancer-cell-targeting nanobody, a fragment of an antibody. By combining these two components, they have created a biomolecule that can specifically target and trim mucins connected to particular cancer cells.

This approach has been tested on lab-grown human cancer cells and in mouse models mimicking human breast and lung cancer. The results, published in Nature Biotechnology, demonstrate that this biomolecule treatment considerably decreased tumour growth and enhanced overall survival. This discovery has wide-ranging potential since mucins are linked to various diseases such as cystic fibrosis, respiratory disorders, and other complications.

This research examined two roles of mucins linked to advancing cancer development. The initial function assists cells in surviving within free-floating "low-adhesion" environments.

The secondary role is to attach to checkpoint receptors, which act like immune system sentinels responsible for examining body cells. A few cancer cells enhance their cell exteriors with mucins covered in distinct sugars that strongly adhere to these receptors. When these sugary mucins connect with checkpoint receptors, they signal that the cancer cell isn't dangerous, preventing the immune system's reaction. As a result, immune cells end up disregarding cancer instead of eliminating it, as they are supposed to do.

Looking ahead, the study's implications for the development of new cancer therapies are promising, although there's still work to be done before implementation in humans. One key future step involves the exploration of creating a targeted mucinase using a protease derived from human sources. This is crucial due to concerns about potential immune responses associated with the non-human-derived enzyme utilised in this study.

In the realm of cancer research, the dawn of bioengineered enzyme-scissors marks a monumental stride towards unveiling previously uncharted avenues for combating cancer resistance. As scientists continue to refine and expand upon these discoveries, the prospect of personalised therapies that circumvent resistance mechanisms emerges as a beacon of hope in the ongoing battle against cancer.