ESR1 and breast carcinoma: Similarly, studies in pre-clinical models of ERα+ breast cancers showed that ABT-263 was ineffective as a single agent, in large part due to rapid Mcl-1 upregulation [17], although the molecular mechanism(s) driving compensatory Mcl-1 upregulation in response to Bcl-2/Bcl-xL inhibition in ER+ breast cancers are not yet clearly defined.