A Case of ALK-Rearranged Adenocarcinoma with Small Cell Carcinoma-Like Transformation and Resistance to Crizotinib

Jin, Yoon; Cho, Byoung Chul; Kim, Hye Ryun; Lee, Hye Jeong; Shim, Hyo Sup

doi:10.1016/j.jtho.2015.12.097

Cited by 70 publications

(41 citation statements)

References 5 publications

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“…Preclinical studies have also suggested that EMT is associated with resistance to crizotinib and ceritinib (43)(44)(45), but clinical specimens were not examined in these reports. Of note, other phenotypic changes, such as transformation to SCLC, have been shown to mediate resistance in EGFR-mutant lung cancer and rarely in ALK-positive NSCLC (36,(46)(47)(48). However, we did not observe transformation to SCLC in any specimens in this series.…”

Section: Discussioncontrasting

confidence: 65%

Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer

Gainor¹,

Dardaei²,

Yoda³

et al. 2016

European Journal of Cancer

163

304

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Section: Discussioncontrasting

confidence: 65%

Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer

Gainor¹,

Dardaei²,

Yoda³

et al. 2016

European Journal of Cancer

163

304

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“…With respect to EGFR-TKIs, 3%–15% of the patients with EGFR -mutated lung cancer develop acquired resistance to EGFR-TKIs by histologic transformation to SCLC 15,16. Similarly, a mechanism underlying SCLC transformation in ALK -positive tumors has been reported in some cases 6–12…”

Section: Discussionmentioning

confidence: 99%

Patients harboring <em>ALK </em>rearrangement adenocarcinoma after acquired resistance to crizotinib and transformation to small-cell lung cancer: a case report

Zhu¹,

Liao²,

Wang³

et al. 2017

OTT

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Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression. Then, next-generation sequencing (NGS) was carried out and detected a TP53 gene mutation, an ALK rearrangement, and no loss of the retinoblastoma gene (RB). Although a regimen for small-cell lung cancer may be one treatment option, a heterogeneous tumor may exist at the time of diagnosis and manifest during the course of disease.

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“…In contrast, histological transformation from adenocarcinoma to SCLC has been reported in several ALK‐TKI‐refractory cases, such as alectinib‐resistant cases. Similar to the SCLC transformation, which is well‐known in EGFR‐TKI‐resistant cases, classic cytotoxic chemotherapy is thought to be effective for overcoming resistance …”

Section: Mechanisms Of Alk‐tki Resistancementioning

confidence: 99%

“…Similar to the SCLC transformation, which is well-known in EGFR-TKI-resistant cases, classic cytotoxic chemotherapy is thought to be effective for overcoming resistance. 73,74 3.3 | Challenges for the future Currently, multiple ALK-TKIs (three in Japan and 4 in the USA) have been approved and are used clinically. In Japan, all three ALK-TKIs have been approved as first-line therapies for ALK-rearranged NSCLC.…”

Section: Bypass Pathway or Other Mechanismmediated Resistancementioning

confidence: 99%

Drug resistance in anaplastic lymphoma kinase‐rearranged lung cancer

Katayama

2018

Cancer Science

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The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled‐coil domain, in the fusion partner that induces abnormal constitutive activation of ALK tyrosine kinase. This results in dysregulated cell proliferation. ALK gene rearrangement has been observed in 3%‐5% of non‐small‐cell lung cancers, and multiple ALK inhibitors have been developed for the treatment of ALK‐positive lung cancer. Among those inhibitors, in Japan, 3 (4 in the USA) ALK tyrosine kinase inhibitors (TKIs) have been approved and are currently used in clinics. All of the currently approved ALK‐TKIs have been shown to induce marked tumor regression in ALK‐rearranged non‐small‐cell lung cancer; however, tumors inevitably relapse because of acquired resistance within a few years. This review focuses on ALK‐TKIs, their resistance mechanisms, and the potential therapeutic strategies to overcome resistance.

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A Case of ALK-Rearranged Adenocarcinoma with Small Cell Carcinoma-Like Transformation and Resistance to Crizotinib

Cited by 70 publications

References 5 publications

Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer

Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer

Patients harboring <em>ALK </em>rearrangement adenocarcinoma after acquired resistance to crizotinib and transformation to small-cell lung cancer: a case report

Drug resistance in anaplastic lymphoma kinase‐rearranged lung cancer

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