Improving on techniques for testing cancer drugs, researchers from IIT Guwahati have come up with silk-protein–based tumour models. An alternative to testing cancer drugs using patient-derived cell lines or animal models, the research involves fabrication of a bio-active composite of silk proteins from two species of silk moths and building a scaffolding that provides a three-dimensional base for growing tumouroids.

Normally, cancer drugs are tested using patient-derived primary cancer cells, on tumours induced in animal models or on genetically modified organisms. However, these models are insufficient to reproduce the three-dimensional morphology and physiology of human tumours and hence show inaccuracies in drug screening. Though animal models are better at this, they can show a variation depending on the species used. Moreover, animal models are expensive to maintain and can increase the cost of drug development. In this context, the silk-protein–based tumour models developed by the group come as a useful intervention.

“As an alternative to existing cancer models, this tissue-engineered 3D silk-based tumour model imitates native tumour microenvironment, complex tumour physiology and metastasis, thus improving drug screening efficacy,” says G. Janani, who is an author of the paper published in Journal of Colloid and Interface Science.

Building scaffolds

The scientists mixed the silk fibroins extracted from the cocoons of the domestic silk moth (Bombyx mori) and the silk glands of the muga silk moth (Antheraea assama) in equal proportions and used them to build up scaffolds on which they grew breast and liver tumour cell cultures. “The Bombyx mori silk fibroin has been well explored for healthcare applications and is also FDA approved,” says Biman B Mandal of IIT Guwahati who led the study, in an email to The Hindu. The A. assama proteins add their own special strength to the scaffolding. As Prof. Mandal explains, “A. assama silk fibroin possesses inherent cell-adhesion RGD ligands [cell attachment sites], which provide better cell attachment and growth conditions in a 3D environment; porosity and tuneable mechanical strength [which] assist in proper nutrient diffusion.”

As a proof of concept, the researchers created breast and liver tumouroids and these showed similar tumour physiology in 3D spatiotemporal arrangements and drug-resistance, as in native solid tumours. They also tested the screening capacity of the tumours on known anticancer drugs, Doxorubicin and Paclitaxel. The tumoroids grown on the silk composite exhibited increased resistance to cancer drugs (as in native conditions) compared to monolayers and spheroids.

Vital step

“The proposed silk scaffold-based in vitro tumour model could serve as a vital step in research laboratories to evaluate a variety of anticancer drugs and understand their mechanisms. The cancer model in the current study demonstrated a better response than monolayer [2D] and spheroid models,” says Prof. Mandal. He qualifies it further, saying, “Still, a [range] of conditions needs to be incorporated and optimised to achieve a high similarity to human cancers. Involving different types of cell such as endothelial cells, cancer stem cells, metastatic cells, etc in the same mileu would closely resemble the human tumour environment.”

The group next plans to miniaturise the cancer model using microfluidics technology and to mimic the native tumour by adding blood vessels in it. “This improved model would assist in studying cancer metastasis from one tissue to another tissue and drug testing for cancer metastasis,” he says.