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Fifty Shades of HOXB7 - Unfolding the Enigma of Tamoxifen Resistance and Metastasis in ER+ Breast Cancer
Abstract
It is still an enigma why breast cancers develop tamoxifen resistance despite ongoing expression of the estrogen receptor and the mystery behind the distant metastasis in these tumors. Several underlying molecular mechanisms that confer resistance and metastasis are understood but a common thread is yet to be discovered. Series of evidence have established homeodomain protein HOXB7 as a master regulatory transcription factor that plays role in angiogenesis, proliferation, invasiveness, migration and drug resistance. The overexpression of HOXB7 in tamoxifen resistant breast cancer patients has prompted the notion that it could be the common thread. In this study, we connected the dots from literature and built a network that elucidates the expanding impact of HOXB7 in both tamoxifen resistance and distant metastasis in ER+ breast cancer cells, making it an attractive therapeutic target. But, due to its extreme homology with other HOX proteins, it has been difficult to achieve a high level of specificity. An intriguing approach to inhibit HOXB7 function could be targeting the upstream regulators of HOXB7. Application of computational biology - designing and synthesizing RNA targeting tools (siRNAs/shRNAs/miRNAs), delivered as nanoparticles for stable, selective, and efficient knockdown, could be a fascinating strategy.
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