Researchers at Albert Einstein College of Medicine have developed a promising strategy to overcome a leading cause of cancer deaths: the ability of cancer cells to survive chemotherapy.

Some cancer cells—called cancer stem cells—can evade chemotherapy and lie dormant. Later, they reactivate, generate new cancer cells, and cause relapse.

In a study published in Nature Communications, investigators used a two‑drug combination to achieve what chemotherapy aims for: forcing cancer cells to self‑destruct through apoptosis, or programmed cell death.  

The treatment worked against human cancer cell lines that resisted apoptosis after multiple types of chemotherapy and against apoptosis‑resistant human tumors implanted in mice.

“We need new, broadly active therapies that can attack a range of cancers while causing fewer side effects, and we hope our new strategy will prove viable,” said Evripidis Gavathiotis, PhD, professor of biochemistry and medicine at Einstein and the paper’s corresponding author.

How apoptosis works

The body uses apoptosis to eliminate unwanted or damaged cells before they become cancerous. Chemotherapy and radiation rely on triggering apoptosis, but cancer cells often resist it.

Each cell contains roughly two dozen apoptotic proteins. Some promote cell death (pro‑apoptotic), while others block it (anti‑apoptotic).

BAX — the executioner protein

The new drug combination kills apoptosis‑resistant cancer cells by boosting the active form of one key pro‑apoptotic protein: BAX, often called the “executioner protein.” Researchers paired their BAX‑activating compound with Navitoclax, an investigational drug that blocks proteins that inhibit BAX.

When the team tested the drug pair on 46 human blood and solid tumor cell lines, it delivered a one‑two punch: the BAX activator drove BAX to toxic levels, and Navitoclax protected it from neutralization.

Limiting side effects

The researchers then tested the combination in mice implanted with colorectal tumor cells that resisted each drug alone but responded when the drugs were combined. Individually, each drug was only moderately effective. Together, they significantly suppressed tumor growth, showing clear synergy.

“Equally important, mice tolerated the two‑drug combination remarkably well,” Dr. Gavathiotis noted. “Healthy cells were not affected—likely making it safer than standard chemotherapies, which are toxic to all dividing cells.”

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