Researchers Find Compounds that Kill Chemo-resistant Cancer Cells

A new study reports the development of compounds that could be used as ovarian cancer treatment. These compounds are particularly promising because they may be able to affect cancer that is resistant to chemotherapy.

The study, “Exploring the Cytotoxicity, Uptake, Cellular Response, and Proteomics of Mono- and Dinuclear DNA Light-Switch Complexes,” was published in Journal of the American Chemical Society.

Chemotherapy remains the first line of treatment for many cancer types, including ovarian cancer, but resistance to chemotherapeutic drugs is a major problem. Some tumors have mutations that make them hard to kill with chemotherapy from the start. Others start off susceptible to chemotherapy but acquire resistance as the cancer cells adapt to the treatment.

“Many cancer cells — about 20% — become resistant to common treatments by learning to ignore the internal signals that tell them to undergo programmed cell death, known as apoptosis,” Jim Thomas, one of the authors of the study, said in a press release.

The newly identified compounds kill cells without activating apoptosis, so the usual mechanisms of resistance don’t work.

The researchers tested their compounds against a panel of cell lines. The tested cells included normal, non-cancerous cells to determine whether the compounds would attack healthy cells, as well as cancer cells resistant and susceptible to chemotherapy, to test for anti-cancer activity.

Two of the compounds — which have long, complicated chemical names — were effective at killing cancer cells, whether or not they were resistant to traditional chemotherapy. Importantly, though, these compounds weren’t especially toxic for non-cancer cells, suggesting that they could be used to kill tumors without causing a lot of damage to the normal cells in the body of a cancer patient.

The researchers then examined the changes in proteins that occurred in cancer cells treated with these compounds with a technique called proteomics, which allowed them to examine the changes in thousands of proteins simultaneously.

This analysis revealed that the compounds acted via two distinct pathways. This will likely be beneficial for treatment because it is less likely that cancer cells will be able to develop resistance in both pathways simultaneously.

The researchers noted that the compounds might be particularly useful for ovarian cancer, in which chemotherapy resistance is especially problematic.

Further studies will be needed to determine whether these compounds are safe and effective to use in living animals, rather than just cells in a lab, before they are used in clinics. The researchers are also hoping to see whether the compounds might be used in combination with current therapies to maximize the effectiveness of treatments.