In recent years, scientists have gradually discovered that the development and progression of many cancers are closely linked to mutations in specific genes. Among them, abnormalities in the KRAS and MYC genes, like a cancer duo, play a key role in many cancers. Now, scientists from the University of North Carolina and other institutions have achieved a significant breakthrough. They have developed a two-in-one molecule that simultaneously targets and silences both cancer-related genes, KRAS and MYC, and precisely delivers the drug directly to tumor cells expressing these genes. This discovery not only offers new hope for treating some difficult-to-treat cancers but also provides new insights into cancer treatment.
KRAS mutations are present in nearly 25% of human cancers, with high frequency in lung cancer (35%), colorectal cancer (49%), and pancreatic cancer (92%). MYC is also a key cancer-related gene, with abnormal MYC function occurring in approximately 50% to 70% of cancers. Abnormal activation of these two genes can promote tumor malignancy through various mechanisms, and therefore, simultaneously targeting both genes has the potential to significantly impact cancer treatment.
In this study, researchers designed a novel inverted chimeric RNA interference (RNAi) molecule that simultaneously silences both the KRAS and MYC genes. RNAi is a cellular process that selectively shuts down or silences mutant genes using small interfering RNA (siRNA). The researchers validated the efficacy of this inverted chimeric RNAi molecule using multiple cell lines and animal models. Compared to using siRNA targeting either KRAS or MYC alone, this "two-in-one" molecule significantly enhanced the inhibitory effect on cancer cell proliferation by up to 40-fold.
Figure 1. Effects of M2/K2 inverted chimeric siRNA on cancer cell viability. (Chareddy Y S, et al., 2025)
In experiments, the researchers tested the activity of this inverted chimeric RNAi molecule in various cancer cell lines through a series of in vitro assays. The results demonstrated that this molecule reduced the expression levels of KRAS and MYC and exerted a strong inhibitory effect on cancer cell proliferation and survival. Experiments in animal models also demonstrated that this molecule effectively inhibited tumor growth and exhibited favorable biodistribution and pharmacokinetic properties.
The researchers noted that this inverted chimeric RNAi molecule simultaneously targeted and silenced two cancer-related genes, KRAS and MYC, and demonstrated significant anti-tumor effects in multiple cancer models. This discovery not only provides an innovative molecular strategy for simultaneously targeting two key cancer genes but also opens new avenues for the development of novel cancer therapeutics. A highlight of this study is the innovative design of a "two-in-one" molecule that simultaneously targets two key cancer genes. This molecule not only demonstrated potent anti-tumor activity in in vitro experiments but also demonstrated favorable efficacy and biodistribution properties in animal models. By simultaneously targeting KRAS and MYC, two key players in cancer, the researchers hope to fundamentally undermine cancer's ability to survive, thereby providing new treatment options for patients.
References
- Stanland L J, et al. A first-in-class EGFR-directed KRAS G12V selective inhibitor. Cancer Cell, 2025.
- Chareddy Y S, et al. Inverted chimeric RNAi molecules synergistically co-target MYC and KRAS in KRAS-driven cancers. The Journal of Clinical Investigation, 2025.