Pancreatic cancer is considered one of the most aggressive and treatment-resistant pathologies in medicine. Researchers have discovered that it is not individual drugs, but a triple combination therapy that works against the tumor. A new study published in PNAS confirms that the simultaneous blocking of all survival pathways leads to the complete destruction of pathological cells.<\/p>\n
Researchers tested the triple therapy against pancreatic ductal adenocarcinoma (PDAC) in mice and patient tumor samples. Scientific experiments showed that a simultaneous strike on the KRAS, EGFR, and STAT3 proteins leads to complete tumor regression and the final cessation of resistance, even in complex cases.<\/p>\n
Genetic analysis confirmed that the joint blocking of RAF1, EGFR, and STAT3 components is necessary for the death of tumor cells. In laboratory conditions, achieving this result became possible through a combination of the drugs: Daraxonrasib, Afatinib, and SD36.<\/p>\n
Overcoming Resistance<\/strong><\/p>\n In 90% of pancreatic adenocarcinoma cases, the KRAS mutation plays a leading role. Although innovative drugs, including Daraxonrasib, significantly increase patients’ life expectancy, tumor cells still develop resistance toward them. Researchers discovered that under conditions of RAF1 and EGFR blocking, the tumor activates an alternative survival pathway, the STAT3 signaling pathway. Consequently, the degradation of the STAT3 protein is considered the turning factor for achieving a sustainable clinical result.<\/p>\n Researchers developed special models in which the Raf1, Egfr, and Stat3 genes were blocked simultaneously. The experiment showed that the apoptosis (death) of resistant cells began only under the condition of synchronous deactivation of all three components. Within the scope of the testing, tumor masses disappeared in 3-4 weeks. It is noteworthy that the mice maintained viability for 300 days, while histological research of the pancreas confirmed the complete elimination of tumor cells and the restoration of tissue structure.<\/p>\n Human Tumor Models (PDX)<\/strong><\/p>\n The study was also conducted on samples taken from seven different patients (PDX models). The triple combination stopped tumor progression in all cases. In less than 60 days, the tumor masses completely disappeared, and no relapse was recorded during the following 80 days. It is significant that the therapy proved to be well-tolerated by the organism, and side effects were maintained at a minimum level.<\/p>\n