Appropriate Therapeutic Options for LOX+ ER– Breast Cancer Patients :
... Briefly, Radiation, Doxorubicin and Mitoxantrone would be ineffective in LOX+ ER– patients.
On the other hand, a PARP1 inhibitor, Cisplatin, Trabectedin and Gemcitabine may Produce Promising Results.
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Overexpression of LOX does present certain advantages. For instance, LOX expression correlates negatively with expression of genes associated with DNA repair (Figure 5A, P = 0.006), but correlates positively with genes down-regulated in samples resistant to Cisplatin, Trabectedin and Gemcitabine (Figure 5B–5D, P 0.0001, P 0.0001, P = 0.002, respectively).
This indicates that cytotoxic drugs such as Cisplatin and Gemcitabine will likely achieve a better clinical response in patients overexpressing LOX. In addition, LOX expression is significantly higher among carriers of BRCA1 mutations than among those without BRCA1 mutation (Figure 6A), though LOX expression does not differ between BRCA2 mutation and wild type carriers (Figure 6B). Since poly (ADP-ribose) polymerase (PARP) inhibitors are effective for treatment of breast cancer patients with BRCA1 mutation [11], this class of drugs may also be effective for managing breast cancer patients who overexpress LOX and carry BRCA1 mutation.
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In sum, our findings show that Radiation, Doxorubin and Mitoxantrone will be less effective in patients overexpressing LOX, but that PARP inhibitors, Cisplatin, Trabectedin and Gemcitabine may yield positive effects.
A limitation of this study is that all the data presented are based on bioinformatics analyses. Still needed are wet lab experiments and well-designed clinical trials before any clinical significance can be attributed.