Targeted Therapies and Drug Resistance in Advanced Breast Cancer, Alternative Strategies and the Way beyond

Simple Summary "Precision medicine" is a therapeutic strategy launched over two decades ago. It relies on drugs that inhibit key molecular mechanisms/pathways or induce anti-tumour effects by modulating immune suppression. During this time, the complexity of advanced breast cancer disease has been increasingly elucidated and many clinical trials, sponsored by multinational drug companies, have been carried out. Nevertheless, patients have seen limited benefits from these clinical trials and the few approved drugs are costly. Concomitant, although other therapeutic strategies have been proposed by researchers over time, the resources available for alternative research have been restrained. As to this, while drug repurposing is an obvious answer to expensive targeted therapies, counteracting micro-metastatic disease represents a new field and seems to be the "way beyond" the current research.Abstract "Targeted therapy" or "precision medicine" is a therapeutic strategy launched over two decades ago. It relies on drugs that inhibit key molecular mechanisms/pathways or genetic/epigenetic alterations that promote different cancer hallmarks. Many clinical trials, sponsored by multinational drug companies, have been carried out. During this time, research has increasingly uncovered the complexity of advanced breast cancer disease. Despite high expectations, patients have seen limited benefits from these clinical trials. Commonly, only a minority of trials are successful, and the few approved drugs are costly. The spread of this expensive therapeutic strategy has constrained the resources available for alternative research. Meanwhile, due to the high cost/benefit ratio, other therapeutic strategies have been proposed by researchers over time, though they are often not pursued due to a focus on precision medicine. Notable among these are drug repurposing and counteracting micrometastatic disease. The former provides an obvious answer to expensive targeted therapies, while the latter represents a new field to which efforts have recently been devoted, offering a "way beyond" the current research.