Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR‐mutated lung adenocarcinoma: a report of two cases

Uruga, Hironori; Fujii, Takeshi; Nakamura, Nobuyuki; Moriguchi, Shuhei; Kishi, Kazuma; Takaya, Hisashi

doi:10.1002/rcr2.521

Cited by 11 publications

(7 citation statements)

References 15 publications

(20 reference statements)

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“…The TKIs may all play a role in the transformation of pathologic types among patients carrying p.T790M. This assumption is consistent with the two cases reported by Uruga et al, 9 which the patients both acquired converted squamous cell carcinoma after taking erlotinib.…”

Section: Discussionsupporting

confidence: 90%

Transformation of advanced lung adenocarcinoma to acquired T790M resistance mutation adenosquamous carcinoma following tyrosine kinase inhibitor: a case report

Liu

Zhang

2020

Tumori

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Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are recommended for patients with non-small cell lung cancer with EGFR mutations. However, acquired resistance to EGFR-TKIs seems inevitable and the mechanism of drug resistance has not been fully defined. There is no effective treatment for patients with advanced lung adenocarcinoma who are resistant to TKIs owing to pathologic type conversion. Case presentation: We report a patient who was initially diagnosed with lung adenocarcinoma. At first, she was sensitive to the first-generation TKI icotinib. After 17 months of treatment, the patient acquired resistance to icotinib. Moreover, after tumor resection, immunohistochemical analysis showed pathologic change from adenocarcinoma to adenosquamous carcinoma, and next-generation sequencing technology discovered EGFR exon19 p.745-750 del, exon20 p.T790M, and KMT2C exon 18 p.R973G mutations. After video-assisted tumor resection, the patient is receiving osimertinib (AZD 9291). Current overall survival is 60 months. Conclusions: Surgical intervention may prolong survival time in patients with acquired TKI resistance, especially when there is no evidence of metastasis.

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Section: Discussionsupporting

confidence: 90%

Transformation of advanced lung adenocarcinoma to acquired T790M resistance mutation adenosquamous carcinoma following tyrosine kinase inhibitor: a case report

Liu

Zhang

2020

Tumori

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“…Significant molecular alterations affecting PI3K-Akt, Wnt, Hippo, mTOR, PDGF (platelet-derived growth factor), and FGF (fibroblast growth factor) signaling pathways are also described [ 23 , 25 , 59 ]. Included among the mutated genes in these pathways are APC , ARID1A , BMPR1A , CHEK2 , DVL1 , EPHB1 , FBXW7 , KDR , MAP2K1 , PDGFRA , PTEN , RB1 , SMARCA4 , SMARCB1 , HRAS , NRAS , and WRN [ 23 , 24 , 59 , 70 , 76 , 77 ], whose genetic alterations have also been found in lung adenocarcinomas [ 78 , 79 , 80 ], colorectal [ 81 , 82 , 83 , 84 ], and breast cancers [ 85 ]. Moreover, oncogenic mutations in ABL1 , EP300 , PIK3CA , PIK3C2B , PTPN11 , and SETDB1 genes [ 23 , 24 , 25 , 59 , 62 ], and novel gains in regions encompassing RHEB , KDM5A , AXIN2 , RICTOR , TRIO , and DVL1 genes were identified [ 24 , 65 ].…”

Section: Genomics Of Malignant Pleural Mesotheliomamentioning

confidence: 99%

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Çakıroğlu

Şentürk

2020

IJMS

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Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.

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“…As shown in Table 2, [10–31] a total of 27 cases of SQ transformation in EGFR mutated lung adenocarcinoma after treatment with EGFR TKIs have been reported. The ages of these patients were 40 to 80 years (median age was 62 years), and 18 patients (66.7%) were female.…”

Section: Discussionmentioning

confidence: 99%

T790M mutation positive squamous cell carcinoma transformation from EGFR-mutated lung adenocarcinoma after low dose erlotinib: A case report and literature review

Kusaba¹,

Takeda²,

Abe³

et al. 2022

Medicine

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Rationale: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of EGFR mutation positive advanced nonsmall cell lung cancer (NSCLC); however, acquired resistance is known to develop during these treatments. Among these mechanisms, histological transformation is seldom encountered. Although platinum based chemotherapy has been reported to be effective in the treatment of patients with small cell lung cancer transformation, there is a lack of information on the treatment of patients with squamous cell carcinoma (SQ) transformation. Patient Concerns and Diagnosis: An 80-year-old nonsmoking woman was referred to our hospital because of an abnormal shadow on her chest radiograph. Diagnostic bronchoscopy was performed and pathological examination revealed adenocarcinoma. Mutation analysis of the EGFR gene revealed deletion of E746-A750 in exon 19. She refused both surgical treatment and radiation therapy, and preferred periodic radiologic follow-up. Unfortunately, approximately a year and a half after the initial diagnosis, the primary lesion enlarged, and many pleural nodules were newly detected (clinically T4N2M1a, stage IVA). Interventions and Outcomes: Based on EGFR mutation analysis, a reduced dose of daily erlotinib was prescribed, which achieved a partial response and 34 months of progression-free survival (PFS). A repeated biopsy with an endobronchial cryoprobe was performed on the enlarged primary lesion. Pathological examination revealed SQ harboring an identical EGFR mutation with a secondary EGFR T790M mutation. Osimertinib 80 mg once a day was started as second line therapy, which resulted in 8 months of PFS and 15 months of survival. Lesson: The literature review and our report suggest that osimertinib is a promising treatment for NSCLC regardless of histology if T790M is present as an acquired mutation.

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Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR‐mutated lung adenocarcinoma: a report of two cases

Cited by 11 publications

References 15 publications

Transformation of advanced lung adenocarcinoma to acquired T790M resistance mutation adenosquamous carcinoma following tyrosine kinase inhibitor: a case report

Transformation of advanced lung adenocarcinoma to acquired T790M resistance mutation adenosquamous carcinoma following tyrosine kinase inhibitor: a case report

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

T790M mutation positive squamous cell carcinoma transformation from EGFR-mutated lung adenocarcinoma after low dose erlotinib: A case report and literature review

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