Researchers are investigating a new form of cell death, called triaptosis, as a potential approach to treating cancer. Traditional treatments such as surgery, chemotherapy, and immunotherapy can fail due to resistant tumor cells that avoid established cell death pathways. Scientists have therefore been seeking alternative ways to target these resilient cancer cells.
A 2024 study published in Science described triaptosis for the first time. According to the study, menadione—a vitamin K precursor—acts as a pro-oxidant that oxidizes the kinase PIK3C3/VPS34. This disrupts endosomal function within the cell, causing an accumulation of vacuoles and eventually leading to plasma membrane rupture and cell death. The process is distinct from previously known forms of programmed cell death.
In mouse models of prostate cancer, oral administration of menadione to induce triaptosis led to better tumor control than standard clinical treatments and had a favorable safety profile.
Associate Professor Lin-Lin Bu and her team at Wuhan University School and Hospital of Stomatology have published a review article titled "Triaptosis and Cancer: Next Hope?" in the journal Research. The article explains the molecular mechanism behind triaptosis, its therapeutic potential, and possible future research directions.
"The mechanism of triaptosis targets a vulnerability inherent in many cancer cells. To sustain rapid proliferation, cancer cells often exhibit a heightened dependence on their endomembrane trafficking system. By specifically disrupting endosomal function, triaptosis may precisely strike this 'Achilles' heel.' Moreover, triaptosis holds considerable promise for combination with immunotherapy. Although its immunogenic potential remains unverified, endosomes play an indispensable role in antigen presentation and immune cell activation. Therefore, inducing triaptosis may not only kill tumor cells but also stimulate a specific antitumor immune response, potentially synergizing with immune checkpoint inhibitors to effectively convert 'cold' tumors into 'hot' ones. Furthermore, since triaptosis operates independently of canonical apoptotic pathways, it may offer a final-line therapeutic option for patients resistant to existing treatments."
The review notes that future research will focus on developing new agents that selectively induce triaptosis and designing drug delivery systems for precise targeting of tumors. Understanding how triaptosis interacts with other types of cell death could also help create more effective combination therapies.
Preliminary evidence suggests that menadione-induced triaptosis might be useful beyond oncology in treating other diseases.
"The discovery of triaptosis not only expands our understanding of fundamental biological processes governing cell death but also represents a promising strategy in the fight against cancer. It is our hope that triaptosis-based therapeutic innovations will soon bridge the gap between bench and bedside, offering renewed hope for cancer patients as the 'next hope' in oncology."
