To capture HER2-positive tumor cell states changes in the presence of PEAK1-expressing MSCs and in response to lapatinib treatment, we performed single-cell Cyclic Immunofluorescence (CycIF) as previously described [26] in combination with the co-culture system described in Fig. 5a (Fig. 8a) across seven unique cell state markers measuring apoptosis evasion (i.e., MCL1), growth signaling (i.e., p-Akt), metastasis (i.e., VIM), DNA damage (i.e., p-γH2AX), oxidative response (i.e., p65NFκB), stress response (i.e., GRP78) and microenvironment fibroblast activation (i.e., αSMA). Here, ACTA1 is linked to neoplasm.