A novel approach to tackling stubborn melanoma draws on the properties of an alternative DNA form, proposed by researchers at the National Research University Higher School of Economics in Russia, in collaboration with colleagues from the United States, China, Australia, and Japan. The concept was detailed in a study published in Nature, signaling a potential shift in how this cancer could be treated in the future.
The focus centers on Z-DNA, a left-handed double-stranded DNA structure that emerges during inflammatory responses and can be triggered by the immune signal interferon. In this mechanism, two proteins, ADAR1 and ZBP1, play pivotal roles. ADAR1 helps modulate the body’s autoimmune reactions, while ZBP1 can drive a cell death program by activating the cell’s self-destruct pathways. These same proteins are present in skin cells that become exposed to cancerous changes, suggesting a direct link between Z-DNA dynamics and tumor biology.
In laboratory experiments, researchers introduced a drug based on CBL0137 molecules into mice bearing melanoma. This compound induces sustained production of Z-DNA, which in turn activates ZBP1 independent of ADAR1. The result was a targeted disruption of fibroblasts that normally support tumor growth, and a renewed responsiveness of cancer cells to immunotherapy. Importantly, this effect appeared to be independent of the specific initial genetic mutation driving the cancer, indicating a potentially broad applicability across different melanoma subtypes.
The authors note that the CBL0137-based therapy has already progressed through several stages of clinical evaluation in humans. While more studies are required to confirm safety and effectiveness, the results point to a possible future where this drug could be integrated into melanoma treatment regimens to enhance immune-mediated tumor control.
Separately, researchers in the United States have explored the strategy of reversing metastatic spread in pancreatic cancer by transferring a patient’s own immune cells to attack tumor cells. In that approach, clinicians ensured that the patient’s T-lymphocytes could recognize a mutant protein expressed by tumor fragments visible on cancer cell surfaces, while avoiding damage to healthy tissues. The early results showed a substantial reduction in metastatic deposits within the lungs within weeks, with further shrinkage observed over subsequent weeks. After an initial rapid response, the metastases remained small for months, suggesting that many of the lesions may have become composed largely of dead or greatly weakened cells. This line of work underscores the potential of autologous immune cell therapies to reshape outcomes in otherwise aggressive cancers.
Building on these advances, the research teams intend to broaden patient participation in trials for these approaches, seeking to determine how best to apply Z-DNA–targeted strategies and autologous immune therapies across diverse cancer types. If ongoing investigations confirm safety and efficacy, such methods could become components of integrated treatment plans that combine precise molecular perturbations with adaptive immune activation to suppress tumor growth and metastasis.