Resumen
Patients with Triple Negative Breast Cancer (TNBC) have a poor prognosis due to high inter-tumor heterogeneity and absence of effective targeted treatments. Through quantification of ongoing processes in each individual with TNBC, we propose an explanation on why certain previously suggested monotherapies, such as anti-EGFR, are not effective. We experimentally demonstrate that monotherapies or drug combinations that are not adjusted accurately to the patient-specific ongoing processes may create an evolutionary pressure on a tumor leading to the emergence of previously undetected or untargeted cellular subpopulations. We show for example that certain TNBC tumors may benefit from therapies targeting estrogen receptors (ER), similarly to ER positive cancers. When untargeted, those tumors may develop large ER positive subpopulations. We propose that anti-TNBC therapy should be accurately tailored to the personalized molecular processes and that incomplete or ?wrong? treatments may generate diverse evolutionary routes of TNBC tumors leading to drug resistance.