Light-activated compound offers hope for overcoming drug resistance in cancer treatment

A research team affiliated with UNIST has unveiled an innovative technology to eliminate drug-resistant cancer cells using light. Professors Tae-Hyuk Kwon and Duyoung Min from the Department of Chemistry at UNIST, alongside Professor Taiho Park from POSTECH, have created a photoreactive compound capable of suppressing autophagy in cancer cells—one of the key mechanisms contributing to resistance against anticancer therapies.

The work is published in the journal Advanced Science.

Cancer cells are known for their remarkable adaptability, posing significant challenges in the development of effective treatments. One of their survival strategies is autophagy, a process in which cells degrade and recycle waste products. This mechanism not only allows cancer cells to expel anticancer drugs but also provides them with energy by repurposing the waste materials, thereby evading immune detection.

To combat this autophagy, the research team designed a photoreactive compound that integrates morpholine and iridium. Morpholine selectively targets cell lysosomes, the organelles where autophagy occurs, while iridium activates upon exposure to light to induce oxidative damage.

In preclinical studies, when this photoreactive compound was administered to mice with drug-resistant pancreatic cancer and subsequently exposed to infrared light, the results were striking. The resistant pancreatic cancer tissues diminished significantly, with complete tumor eradication observed within just seven days.

Analysis revealed that the compound, upon light activation, disrupted the lysosomal membrane and prevented its fusion with autophagosomes—structures responsible for isolating cellular waste. The research team noted that they plan to investigate additional proteins involved in this oxidative damage process.

Mingyu Park from the Department of Chemistry served as the lead researcher on this study, with O2Medi Co., Ltd. conducting assessments of toxicity and anticancer efficacy using an animal model.

Professor Kwon remarked, “This groundbreaking approach to targeting autophagy could significantly enhance treatment options for major intractable cancers that exhibit drug resistance. We are also exploring the efficacy of combination therapies that incorporate existing anticancer agents alongside gemcitabine.”