<p>Breast cancer is the most prevalent form of cancer affecting women across the globe. Among its subtypes, Triple-Negative Breast Cancer (TNBC) poses a significant challenge due to its aggressive nature, lack of targeted therapies, and inherent radioresistance. TNBC is characterized by the absence of three key receptors: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor, making it unresponsive to available therapies. This, coupled with its aggressive nature and radioresistance, underscores the urgent need for novel therapeutic strategies. This study investigates the therapeutic potential of two natural compounds, Andrographolide and Melatonin, in TNBC treatment, with a focus on their interactions with the MYC protein, a common transcription factor implicated in TNBC. The research methodology involved a combination of in silico and in vitro analyses. In silico molecular docking and molecular dynamics simulations were used to explore the potential interactions of Andrographolide and Melatonin with MYC. The results indicate that both compounds exhibit stable binding to MYC and may influence the expression of genes associated with DNA repair and cell cycle regulation. Preliminary in vitro data suggest potential radiosensitizing effects when used in combination with ionizing radiation. While these findings are exploratory in nature, they provide initial insights into MYC modulation as a possible strategy to enhance radiation response in TNBC. Further preclinical studies are warranted to evaluate the therapeutic potential of these compounds in combination with radiotherapy.</p>