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108. Martín Martorell P, Huerta M, Compañ Quilis A, Abellán R, Seda E, Blesa S, Chaves FJ, Dualde Beltrán D, Roselló Keränen S, Franco J, Insa A. Coexistence of EGFR, KRAS, BRAF, and PIK3CA mutations and ALK rearrangement in a comprehensive cohort of 326 consecutive Spanish nonsquamous NSCLC patients. Clin Lung Cancer 2017;18:e395-402.

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112. Lin L, Asthana S, Chan E, Bandyopadhyay S, Martins MM, Olivas V, Yan JJ, Pham L, Wang MM, Bollag G, Solit DB, Collisson EA, Rudin CM, Taylor BS, Bivona TG. Mapping the molecular determinants of BRAF oncogene dependence in human lung cancer. Proc Natl Acad Sci U S A 2014;111:E748-57.

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114. Yamamoto C, Basaki Y, Kawahara A, Nakashima K, Kage M, Izumi H, Kohno K, Uramoto H, Yasumoto K, Kuwano M, Ono M. Loss of PTEN expression by blocking nuclear translocation of EGR1 in gefitinib-resistant lung cancer cells harboring epidermal growth factor receptor-activating mutations. Cancer Res 2010;70:8715-25.

115. Sos ML, Koker M, Weir BA, Heynck S, Rabinovsky R, Zander T, Seeger JM, Weiss J, Fischer F, Frommolt P, Michel K, Peifer M, Mermel C, Girard L, Peyton M, Gazdar AF, Minna JD, Garraway LA, Kashkar H, Pao W, Meyerson M, Thomas RK. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res 2009;69:3256-61.

116. Kokubo Y, Gemma A, Noro R, Seike M, Kataoka K, Matsuda K, Okano T, Minegishi Y, Yoshimura A, Shibuya M, Kudoh S. Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA). Br J Cancer 2005;92:1711-9.

117. Shepherd FA, Lacas B, Le Teuff G, Hainaut P, Jänne PA, Pignon JP, Le Chevalier T, Seymour L, Douillard JY, Graziano S, Brambilla E, Pirker R, Filipits M, Kratzke R, Soria JC, Tsao MS; LACE-Bio Collaborative Group. Pooled analysis of the prognostic and predictive effects of TP53 comutation status combined with KRAS or EGFR mutation in early-stage resected non–small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol 2017;35:2018-27.

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120. You B, Yang YL, Xu Z, Dai Y, Liu S, Mao JH, Tetsu O, Li H, Jablons DM, You L. Inhibition of ERK1/2 down-regulates the hippo/YAP signaling pathway in human NSCLC cells. Oncotarget 2015;6:4357-68.

121. McGowan M, Kleinberg L, Halvorsen AR, Helland Å, Brustugun OT. NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors. Genes Cancer 2017;8:497-504.

122. Hsu PC, You B, Yang YL, Zhang WQ, Wang YC, Xu Z, Dai Y, Liu S, Yang CT, Li H, Hu B, Jablons DM, You L. YAP promotes erlotinib resistance in human non-small cell lung cancer cells. Oncotarget 2016;7:51922-33.

123. Ghiso E, Migliore C, Ciciriello V, Morando E, Petrelli A, Corso S, De Luca E, Gatti G, Volante M, Giordano S. YAP-dependent AXL overexpression mediates resistance to EGFR inhibitors in NSCLC. Neoplasia 2017;19:1012.

124. Galvani E, Sun J, Leon LG, Sciarrillo R, Narayan RS, Sjin RT, Lee K, Ohashi K, Heideman DA, Alfieri RR, Heynen GJ, Bernards R, Smit EF, Pao W, Peters GJ, Giovannetti E. NF-κB drives acquired resistance to a novel mutant-selective EGFR inhibitor. Oncotarget 2015;6:42717-32.

125. Voortman J, Checińska A, Giaccone G. The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells. Mol Cancer 2007;6:73.

126. Voortman J, Pham TV, Knol JC, Giaccone G, Jimenez CR. Prediction of outcome of non-small cell lung cancer patients treated with chemotherapy and bortezomib by time-course MALDI-TOF-MS serum peptide profiling. Proteome Sci 2009;7:34.

127. Ceresa C, Giovannetti E, Voortman J, Laan AC, Honeywell R, Giaccone G, Peters GJ. Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics and pharmacodynamics in non-small cell lung cancer and blood mononuclear cells. Mol Cancer Ther 2009;8:1026-36.

128. Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA. Genotyping and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011;3:75ra26.

129. Zakowski MF, Ladanyi M, Kris MG; Memorial Sloan-Kettering Cancer Center Lung Cancer OncoGenome Group. EGFR mutations in small-cell lung cancers. N Engl J Med 2006;355:213-5.

130. Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol 2015;16:e165-72.

131. Lee JK, Lee J, Kim S, Kim S, Youk J, Park S, An Y, Keam B, Kim DW, Heo DS, Kim YT, Kim JS, Kim SH, Lee JS, Lee SH, Park K, Ku JL, Jeon YK, Chung DH, Park PJ, Kim J, Kim TM, Ju YS. Clonal history & genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas. J Clin Oncol 2017;35:3065-74.

132. Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015;6:6377.

133. Lemos C, Jansen G, Peters GJ. Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors. Br J Cancer 2008;98:857-62.

134. Da Silva CG, Honeywell RJ, Dekker H, Peters GJ. Physicochemical properties of novel protein kinase inhibitors in relation to their substrate specificity for drug transporters. Expert Opin Drug Metab Toxicol 2015;11:703-17.

135. Porcelli L, Lemos C, Peters GJ, Paradiso A, Azzariti A. Intracellular trafficking of MDR transporters and relevance of SNPs. Curr Top Med Chem 2009;9:197-208.

136. Elkind NB, Szentpétery Z, Apáti A, Ozvegy-Laczka C, Várady G, Ujhelly O, Szabó K, Homolya L, Váradi A, Buday L, Kéri G, Német K, Sarkadi B. Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor iressa (ZD1839, Gefitinib ) multidrug transporter ABCG2 prevents tumor cell death induced. Cancer Res 2005;65:1770-7.

137. Brózik A, Hegedüs C, Erdei Z, Hegedus T, Özvegy-Laczka C, Szakács G, Sarkadi B. Tyrosine kinase inhibitors as modulators of ATP binding cassette multidrug transporters: substrates, chemosensitizers or inducers of acquired multidrug resistance? Expert Opin Drug Metab Toxicol 2011;7:623-42.

138. Yanase K, Tsukahara S, Asada S, Ishikawa E, Imai Y, Sugimoto Y. Gefitinib reverses breast cancer resistance protein-mediated drug resistance. Mol Cancer Ther 2004;3:1119-25.

139. Nakamura Y, Oka M, Soda H, Shiozawa K, Yoshikawa M, Itoh A, Ikegami Y, Tsurutani J, Nakatomi K, Kitazaki T, Doi S, Yoshida H, Kohno S. Gefitinib (“Iressa”, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, reverses breast cancer resistance protein/ABCG2-mediated drug resistance. Cancer Res 2005;65:1541-6.

140. Marchetti S, de Vries NA, Buckle T, Bolijn MJ, van Eijndhoven MA, Beijnen JH, Mazzanti R, van Tellingen O, Schellens JH. Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther 2008;7:2280-7.

141. Lemos C, Kathmann I, Giovannetti E, Calhau C, Jansen G, Peters GJ. Impact of cellular folate status and epidermal growth factor receptor expression on BCRP/ABCG2-mediated resistance to gefitinib and erlotinib. Br J Cancer 2009;100:1120-7.

142. Wind S, Schnell D, Ebner T, Freiwald M, Stopfer P. Clinical pharmacokinetics and pharmacodynamics of afatinib. Clin Pharmacokinet 2017;56:235-50.

143. Kazmi F, Hensley T, Pope C, Funk RS, Loewen GJ, Buckley DB, Parkinson A. Lysosomal sequestration (trapping) of lipophilic amine (cationic amphiphilic) drugs in immortalized human hepatocytes (Fa2N-4 cells). Drug Metab Dispos 2013;41:897-905.

144. Nadanaciva S, Lu S, Gebhard DF, Jessen BA, Pennie WD, Will Y. A high content screening assay for identifying lysosomotropic compounds. Toxicol Vitr 2011;25:715-23.

145. Zhitomirsky B, Assaraf YG. Lysosomal sequestration of hydrophobic weak base chemotherapeutics triggers lysosomal biogenesis and lysosome-dependent cancer multidrug resistance. Oncotarget 2015;6:1143-56.

146. Honeywell R, Yarzadah K, Giovannetti E, Losekoot N, Smit EF, Walraven M, Lind JS, Tibaldi C, Verheul HM, Peters GJ. Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 2010;878:1059-68.

147. Van Der Steen N, Honeywell RJ, Dekker H, Van Meerloo J, Kole J, Musters R, Ruijtenbeek R, Rolfo C, Pauwels P, Peters GJ, Giovannetti E. Resistance to crizotinib in a cMET gene amplified tumor cell line is associated with impaired sequestration of crizotinib in lysosomes. J Mol Clin Med 2018;1:101-8.

148. Gotink KJ, Broxterman HJ, Labots M, de Haas RR, Dekker H, Honeywell RJ, Rudek MA, Beerepoot LV, Musters RJ, Jansen G, Griffioen AW, Assaraf YG, Pili R, Peters GJ, Verheul HM. Lysosomal sequestration of sunitinib: a novel mechanism of drug resistance. Clin Cancer Res 2011;17:7337-46.

149. Gotink KJ, Rovithi M, de Haas RR, Honeywell RJ, Dekker H, Poel D, Azijli K, Peters GJ, Broxterman HJ, Verheul HM. Cross-resistance to clinically used tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib. Cell Oncol (Dordr) 2015;38:119-29.

150. Zhitomirsky B, Assaraf YG. Lysosomal accumulation of anticancer drugs triggers lysosomal exocytosis. Oncotarget 2017;8:45117-32.

151. Honeywell RJ, Hitzerd S, Kathmann I, Peters GJ. Transport of six tyrosine kinase inhibitors: active or passive? ADMET & DMPK 2016;4:23-34.

152. Galvani E, Peters GJ, Giovannetti E. Thymidylate synthase inhibitors for non-small cell lung cancer. Expert Opin Investig Drugs 2011;20:1343-56.

153. Rolfo C, Caglevic C, Santarpia M, Araujo A, Giovannetti E, Gallardo CD, Pauwels P, Mahave M. Immunotherapy in NSCLC: a promising and revolutionary weapon. Adv Exp Med Biol 2017;995:97-125.

154. Avan A, Narayan R, Giovannetti E, Peters GJ. Role of Akt signaling in resistance to DNA-targeted therapy. World J Clin Oncol 2016;7:352-69.

155. Giovannetti E, Lemos C, Tekle C, Smid K, Nannizzi S, Rodriguez JA, Ricciardi S, Danesi R, Giaccone G, Peters GJ. Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multitargeted antifolate pemetrexed in non-small-cell lung cancer cells. Mol Pharmacol 2008;73:1290-300.

156. Avan A, Adema AD, Hoebe EK, Huijts CM, Avan A, Veal GJ, Ruijtenbeek R, Wosikowski K, Peters GJ. Modulation of signaling enhances the efficacy of the combination of satraplatin and erlotinib. Curr Drug Targets 2014;15:1312-21.

157. Narayan RS, Fedrigo CA, Brands E, Dik R, Stalpers LJ, Baumert BG, Slotman BJ, Westerman BA, Peters GJ, Sminia P. The allosteric AKT inhibitor MK2206 shows a synergistic interaction with chemotherapy and radiotherapy in glioblastoma spheroid cultures. BMC Cancer 2017;17:204.

Cancer Drug Resistance
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