Research News
Sequential Drug Combo Shows Promise Against Aggressive Breast Cancer
A recent study has uncovered a synergistic effect when doxorubicin (DOX) is administered before zoledronic acid (ZA) in estrogen receptor-negative (ER-negative) breast cancer cells. This finding is particularly significant given that ER-negative breast cancer, including triple-negative breast cancer (TNBC), is often aggressive and lacks specific treatment targets.
Zoledronic acid is commonly used in breast cancer patients to manage bone metastases and related complications. While it has shown some anti-cancer effects, its optimal use, especially in combination with chemotherapy, has been an area of ongoing research. This study, published in Naunyn-Schmiedeberg Archives of Pharmacology, explored the effects of both sequential and nonsequential administration of ZA and DOX on ER-positive and ER-negative breast cancer cell lines.
A significant synergistic effect was observed only when DOX was administered sequentially before ZA in ER-negative breast cancer cells. This was not seen in ER-positive cells or with nonsequential treatment in ER-negative cells. The sequential DOX-then-ZA treatment significantly reduced cell invasion in ER-negative cells. This is crucial as ER-negative breast cancers are highly invasive and metastatic. This synergistic sequential treatment also significantly reduced the protein levels of MMP9, pNF-$kappa$B, and FGF2 in ER-negative cells. These proteins are vital mediators of cell invasion, metastasis, and angiogenesis (new blood vessel formation that feeds tumors).
The research suggests that DOX pretreatment primes ER-negative cells, increasing their sensitivity to ZA and enhancing its cytotoxic effects. ZA is thought to inhibit the canonical NF-$kappa$B pathway, which in turn suppresses MMP9 and indirectly inhibits FGF2, thereby hindering cell invasion and angiogenesis.
These findings suggest a potential strategy to enhance anticancer effects, including antiproliferative and anti-invasive actions, particularly in aggressive ER-negative breast cancers. By optimizing the drug administration sequence, it might be possible to reduce DOX dosages and exposure durations, thereby minimizing severe side effects like cardiotoxicity.
This study provides a scientific basis for optimizing chemotherapy regimens for ER-negative breast cancer, potentially leading to more effective treatments with reduced adverse effects. Future research should focus on validating these findings in in vivo models and clinical trials.
This publication received an award for graduate students who completed their studies on time and had international publications, 1st time, Academic Year 2567.
- Ratchadaphiseksomphot Fund, Graduate Affairs, Faculty of Medicine, Chulalongkorn University (Grant No. GA 67/033)