Lapatinib

MCF7, BT549, MDAMB231, MDAMB468, Hs578T, SUM159PT, BT549, and BT20 breast cancer cell lines were obtained from ATCC (Manassas, VA, USA). MCF7 cells were grown in DMEM medium, the other cell lines were grown in RPMI medium, with 10% fetal bovine serum (FBS), penicillin (100 U/mL), and streptomycin (100 µg/mL). Cells were plated 24 h before treatment with different drugs at the indicated concentrations. Recombinant human EGF, heregulin (HRG), IGF1, angiotensin II (Ang II), and angiotensin 1–7 (Ang 1–7) were obtained from Sigma Chemical Co (St. Louis, MO, USA). Recombinant HGF and FGF were from Abcam. Recombinant PDGF-BB was from Gibco. Trastuzumab, gifitinib, lapatinib, sunitinib, OSI-906, and doxorubicin were obtained from Selleck Chemicals. The PRCP inhibitor (PRCP-7414, referred to as PRCPi in text) was from Calbiochem (catalog number 504044).

Gentamicin sulfate, dimethyl sulfoxide (DMSO), Triton X-100 (used at 1%), mTOR inhibitor rapamycin (used at 1 μM) and bafilomycin A1 (used at 100 nM) were all purchased from Sigma-Aldrich (Merck, Darmstadt, Germany). Sapitinib (AZD8931) and lapatinib were ordered from Selleck Chemicals (Houston, TX, USA) and SignalChem (Richmond, BC, Canada), respectively. Kinase inhibitors from the published kinase inhibitor sets (PKIS)1 and PKIS2 were kindly provided by GlaxoSmithKline Global Health Medicines R&D (GSK) and the Structural Genomics Consortium of the University of North Carolina at Chapel Hill (SGC-UNC) (Elkins et al., 2016 (link); Drewry et al., 2017 (link)). Larger quantities of GW296115X were obtained from AOBIOUS (Gloucester, MA, USA). All PKIS compounds were dissolved in DMSO at 10 mM. Adenosine monophosphate-activated protein kinase (AMPK) activator compound 991 (ex229) (Xiao et al., 2013 (link)) (Spirochem, Basel, Switzerland; used at 25 μM) was kindly shared by Eline Brombacher and Dr. Bart Everts (Leiden university Medical Center, Leiden, Netherlands). Chemical structures were generated from published simplified molecular-input line-entry specification (SMILES) using ChemDraw (PerkinElmer, Waltham, MA, USA).

MCF7 breast cancer cell line was obtained from ATCC. MCF7 cells were grown in DMEM medium, with 10% fetal bovine serum (FBS), penicillin (100 U/mL) and streptomycin (100 µg/mL). Cells were plated 24 h before treatment with different drugs at the indicated concentrations.^{27 (link)} Recombinant human heregulin (HRG) and IGF1 were obtained from Sigma Chemical Co (St. Louis, MO).^{27 (link)} PRCP inhibitor (PRCP-7414); catalog number 504044 was from Calbiochem. OSI906 and lapatinib are obtained from Selleckchem.

The breast cancer cell lines MCF‐7, MDA‐MB‐231, MDA‐MB‐468 and HCC1954 were maintained in RPMI‐1640 plus GlutaMAX‐1 (Gibco) supplemented with 10% fetal calf serum (FCS) and 10 µg/ml insulin. HEK293T cells were maintained in DMEM (Gibco) plus 10% FCS. JQ1, I‐BET762 and I‐BET151 were purchased from Cayman Chemical (Ann Arbor, MI, USA). Trametinib, olaparib, palbociclib, alisertib, dasatinib, 17‐AAG, lapatinib, trastuzumab, cycloheximide (CHX) and Mcl‐1 inhibitors (S63845 and TW‐37) were commercially sourced from Selleckchem (Houston, TX, USA).

5-Fluorouracil, oxaliplatin and irinotecan were obtained from the pharmacy of the University of Campania “Luigi Vanvitelli”. Cetuximab, panitumumab, SYM004, MM151, trastuzumab, pertuzumab and duligotuzumab antibodies were kindly provided by Merck, Amgen, Symphogen, Merrimack Pharmaceuticals, Roche and Genentech, respectively. Refametinib, a selective MEK 1/2 inhibitor was kindly provided by Bayer Italy; Pictilisib, a PI3Kα inhibitor and lapatinib were purchased from Selleckchem.