AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment. The inhibitors were evaluated in breast cancer for both cytotoxicity and metabolic stability assays across both murine and human breast cancer cell lines. Both AQP inhibitors also affected the expression of other AQP transcripts and proteins, which demonstrates compensatory regulation between AQP family members. As a single agent, Auphen treatment in vivo extended overall survival but did not impact primary or metastatic tumor burden. However, Auphen treatment made cells more responsive to chemotherapy (doxorubicin) or endocrine treatment (tamoxifen, fulvestrant). In fact, treatment with Tamoxifen reduced overall AQP7 protein expression. RNA-seq of breast cancer cells treated with Auphen identified mitochondrial metabolism genes as impacted by Auphen and may contribute to reducing mammary tumor progression, lung metastasis, and increased therapeutic efficacy of endocrine therapy in breast cancer. Interestingly, we found that Auphen and tamoxifen cooperate to reduce breast cancer cell viability, which suggests that Auphen treatment makes the cells more susceptible to Tamoxifen. Together, this study highlights AQPs as therapeutic vulnerabilities of breast cancer metastasis that are promising and should be exploited. However, the pharmacologic results suggest additional chemical refinements and optimization of AQP inhibition are needed to make these AQP inhibitors appropriate to use for therapeutic benefit in overcoming endocrine therapy resistance.

Gene editing, spearheaded by the CRISPR/Cas9 system, has revolutionized biotechnology by enabling precise modifications, with applications impacting agriculture, biomedicine, and industrial biotechnology. Our review proposal analyzes the evolution from ZFN and TALEN nucleases to advanced base editors and prime editing, which increase precision without requiring double-strand breaks. In the agri-food sector, improvements in yield, nutritional quality, and climate resilience stand out, including the de novo domestication of wild species. Furthermore, its potential to optimize industrial bioprocesses and drug development within the global bioeconomy is explored. However, commercial success depends on overcoming bottlenecks and harmonizing regulatory frameworks that vary across product- and process-based approaches. The convergence of gene editing and computational analysis (Artificial Intelligence) promises to usher in a new era of biotechnological innovation.