At a cellular level, traditional strategies for treating cancer are like molecular battlefields. Chemotherapies penetrate the membranes of rapidly dividing cells in a bid to combat tumors. However, the tumors often fight back. Cancerous cells develop genes over time, which can pump out anticancer drugs, rendering the therapies ineffective.
To regain control in the battle against drug resistance, clinicians sometimes treat patients with a slew of chemotherapy drugs. Despite its combination of distinct cell-killing pathways, such a strategy is not always successful in destroying particularly resilient cancer cells.
A team of researchers led by Yi Yan Yang, Covering Executive Director of A*STAR’s Institute of Bioengineering and Bioimaging (IBB), found a novel approach to tackle the problem of cancer drug resistance. The team set out to explore the possibility of disrupting cancer cell’s negatively charged membrane with the help of positively charged biopolymers.
“The cationic biopolymer can disrupt cancer cell membrane to increase the entry of chemotherapeutics into cancer cells, including chemotherapeutic-resistant cells,” explained Yang, adding that this would help restore the potency of clinically available cancer chemotherapeutics.
Yang and colleagues had previously developed a novel quaternary ammonium-functionalized polycarbonate polymer, which was able to destroy both bacterial and cancer cells on its own. In the current study, the team tested the synergistic tumor-killing effects of the polymer in combination with existing chemotherapeutics and repurposed antibiotics.
Using a drug-resistant cancer cell line, they found that their polymer made the cells three to 10 times more sensitive to the effects of the drugs. In theory, this would significantly reduce the dose of chemotherapeutic agents required to combat tumors. “The cationic biopolymer can be paired with a wide range of drugs to reduce toxicity and overcome resistance,” said Yang.
Moving forward, the team plans to commercialize its technology by collaborating with industry partners. Together, Yang and her colleagues are set to further optimize the polymer formulation before testing it in animal studies and eventually, in clinical trials.
“The use of biopolymers to enhance drug efficiencies against difficult oncological targets represents an emerging paradigm in cancer treatment,” Yang said. “Instead of the costly process of bringing new cancer drugs to market, these biopolymers could help breathe new life into existing off-the-shelf therapies.”
The A*STAR-affiliated researchers contributing to this research are from the Institute of Bioengineering and Bioimaging (IBB).