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|Authors||Catino A, Lacalamita R, De Summa S, Pesola F, Tommasi S, Galetta D|
|Title||Multiple Genetic Alterations as Resistance Mechanism during Second-Line Lorlatinib for Advanced ALK-Rearranged Lung Adenocarcinoma: A Case Report.|
|Journal||Diagnostics (Basel, Switzerland)|
|Date||2022 Mar 11|
|Abstract Text||Second and third-generation ALK-TKI inhibitors have showed better activity and have replaced crizotinib in most of cases of advanced ALK-rearranged lung adenocarcinoma. The emergence of resistance adversely affects also the activity of these newer drugs; in particular, lorlatinib often shows multiple and complex resistance mechanisms. The case reported here highlights the importance of reassessing the biomolecular profile during the disease course, both by tissutal and liquid biopsy, with the aim of improving the knowledge of these resistance mechanisms, and so identifying new drugs or sequences able to optimize the management of these patients.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|EML4 - ALK ALK G1202R||lung adenocarcinoma||predicted - sensitive||Lorlatinib||Case Reports/Case Series||Actionable||In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R (PMID: 35328235).||35328235|
|EML4 - ALK ALK G1202R||lung adenocarcinoma||predicted - resistant||Alectinib||Case Reports/Case Series||Actionable||In a clinical case study, ALK G1202R was identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) after the disease progressed on Alecensa (alectinib) treatment (PMID: 35328235).||35328235|
|EML4 - ALK ALK T1151K ALK G1202R ALK S1206F||lung adenocarcinoma||predicted - resistant||Lorlatinib||Case Reports/Case Series||Actionable||In a clinical case study, ALK S1206F and ALK T1151K were identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R after the disease progressed on Lorbrena (lorlatinib) treatment (PMID: 35328235).||35328235|