Resistance to therapy through adaptation by tumors poses a major hurdle for cancer therapy. Bioengineers have worked to address this by creating a single nanoparticle that comprises a synergistic drug pair that shuts down mechanisms of resistance to a degree that has not been achieved before, according to preclinical findings.1
Even aggressive treatments such as immunotherapies or nanomedicines may fail to eliminate all cancer cells, allowing new mutations to develop that may cause relapse. This team, based at Brigham and Women’s Hospital, Boston, Massachusetts, stated that combination therapies are not always successful and that they lead to resistance because of the spatial proximity of each drug in the combination pair. The success of the 2-in-1 nanoparticle has implications for how combination therapy is administered in the clinic and the use of complementary drug pairs for the treatment of cancer.
The team used computational approaches to design a supramolecular nanotherapeutic that tied together 2 cancer therapies: the chemotherapy drug docetaxel and a targeted therapy known as a PI3K inhibitor. With a single structure that paired the 2 drugs, both therapeutic agents could be delivered to the same cells, which more effectively eliminated cancer cells in preclinical models and resulted in greater tumor inhibition.
“We were inspired by the mathematical understanding that a cancer cell rewires the mechanisms of resistance in a defined way,” said Aaron Goldman, PhD, of Brigham and Women’s Hospital Renal Division. “By developing a 2-in-1 nanomedicine, we could ensure the same cell that was acquiring this new resistance saw the lethal drug combination, shutting down the survival program and eliminating the evidence of resistance. This 2-in-1 method could redefine how clinicians deliver the ‘1-2 punch’ combination of drugs.”
1. Goldman A, Kulkarni A, Kohandel M, et al. Rationally Designed 2-in-1 Nanoparticles Can Overcome Adaptive Resistance in Cancer. ACS Nano. 2016; 10(6):5823-5834.