lorlatinib-resistant ALK mutants don't bind lorlatinib

Stable Identifier
Reaction [transition]
Homo sapiens
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The following ALK mutants are resistant to inhibition by lorlatinib:

ALK I1171N: Ouseph et al, 2019
ALK I1171S: Takahashi et al, 2020
ALK L1196M: Yoda et al, 2018
ALK L1198F: Yoda et al, 2018
ALK G1202R: Kougioumtzi et al, 2019
ALK G1269A: Kougioumtzi et al, 2019; Takahashi et al, 2020; Yoda et al, 2018

Literature References
PubMed ID Title Journal Year
31943796 Overcoming resistance by ALK compound mutation (I1171S + G1269A) after sequential treatment of multiple ALK inhibitors in non-small cell lung cancer

Uchibori, K, Yanagitani, N, Tsukahara, M, Okubo, K, Nishio, M, Seto, Y, Okada, K, Takahashi, K, Oh-Hara, T, Uematsu, S, Fujita, N, Katayama, R

Thorac Cancer 2020
31616196 TKI-resistant ALK-rearranged lung adenocarcinoma with secondary CTNNB1 p.S45V and tertiary ALK p.I1171N mutations

Patel, NR, Khurshid, H, Ali, SM, Aswad, BI, Resnick, MB, Yakirevich, E, Ouseph, MM, Taber, A, Madison, R

Lung Cancer (Auckl) 2019
29650534 Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound ALK Mutations in ALK-Positive Lung Cancer

Mino-Kenudson, M, Friboulet, L, Benes, CH, Engelman, JA, Yoda, S, Gainor, JF, Dardaei, L, Iafrate, AJ, Heist, RS, Shaw, AT, Dagogo-Jack, I, Langenbucher, A, Burke, BJ, Hata, AN, Ferris, LA, Timonina, D, Johnson, TW, Hubbeling, H, Timofeevski, S, Lawrence, MS, Kattermann, KE, Lin, JJ, Prutisto-Chang, K, Riley, AK, Lennerz, JK

Cancer Discov 2018
31749991 Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review

Kampletsas, E, Ntellas, P, Nasioulas, G, Papadopoulou, E, Kougioumtzi, A, Pentheroudakis, G

ESMO Open 2019
Normal reaction
Functional status

Loss of function of lorlatinib-resistant ALK mutants [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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