A study reveals that mitochondrial transfer (MT) from adipose stem cells (ASCs) to breast cancer cells (BCCs) promotes multi-drug resistance (MDR). The research demonstrates that MT occurs via tunneling nanotubes (TNTs) and is influenced by actin polymerization. The transferred mitochondria from ASCs enhance ATP production, which drives ABC transporter-mediated drug efflux, leading to increased resistance to chemotherapy. The study also shows that blocking MT can restore drug sensitivity in BCCs, suggesting it as a potential therapeutic target for breast cancer treatment. The findings highlight the role of the tumor microenvironment in cancer progression and treatment resistance, emphasizing the importance of mitochondrial dynamics in cancer cell metabolism and drug response. The study used various models, including patient-derived organoids and co-cultures, to investigate the mechanisms of MT and its impact on cancer cell behavior. The results indicate that mitochondrial transfer from ASCs to BCCs is a significant factor in the development of drug resistance, and targeting this process could lead to new treatment strategies for breast cancer.A study reveals that mitochondrial transfer (MT) from adipose stem cells (ASCs) to breast cancer cells (BCCs) promotes multi-drug resistance (MDR). The research demonstrates that MT occurs via tunneling nanotubes (TNTs) and is influenced by actin polymerization. The transferred mitochondria from ASCs enhance ATP production, which drives ABC transporter-mediated drug efflux, leading to increased resistance to chemotherapy. The study also shows that blocking MT can restore drug sensitivity in BCCs, suggesting it as a potential therapeutic target for breast cancer treatment. The findings highlight the role of the tumor microenvironment in cancer progression and treatment resistance, emphasizing the importance of mitochondrial dynamics in cancer cell metabolism and drug response. The study used various models, including patient-derived organoids and co-cultures, to investigate the mechanisms of MT and its impact on cancer cell behavior. The results indicate that mitochondrial transfer from ASCs to BCCs is a significant factor in the development of drug resistance, and targeting this process could lead to new treatment strategies for breast cancer.