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Over the past decade, significant advances have been achieved in the diagnostic testing, treatment, and prognosis of advanced non–small-cell lung cancer (NSCLC). One of the most significant developments was the identification of specific gene alterations that define subsets of NSCLC. In 2007, ROS1 rearrangements were first described and observed in approximately 1%-2% of patients with NSCLC. Currently, crizotinib remains the therapy of choice for advanced ROS1-rearranged NSCLC without CNS metastases, while entrectinib has emerged as the preferred option for those with CNS metastases. The next-generation inhibitors under development are more potent, have better CNS efficacy, and can overcome important resistance mutations. In this review, we focus on the management of patients with advanced NSCLC harboring a ROS1 rearrangement. We aim to provide insight into the diagnosis, treatment approach, and emerging treatments in this subgroup of NSCLC.

AIMS Spitzoid tumours have been shown to harbour exclusive kinase fusions. Few studies have analysed substantial numbers of ROS1-rearranged lesions. The aim of the present study was to investigate also their immunohistochemical profile. METHODS AND RESULTS Among a group of 35 spitzoid tumours, of which 34 were consecutively diagnosed in a 3-year period, we found 11 ROS1 cases that were immunohistochemically positive, from 10 patients, eight of whom were female and two of whom were male, and who were aged 3-52 years (median, 29 years); most lesions (eight) were localized on the lower extremities. Four patterns of immunostaining were observed: cytoplasmic granular diffuse (six cases), sparse cytoplasmic granules (three cases), paranuclear dots (one case), and nuclear (one case). Fluorescence in-situ hybridisation (FISH) analysis showed all cases to be rearranged (cut-off of >15%). RNA next-generation sequencing (NGS) analysis showed specific fusions of ROS1 in four cases: two with PWWP2A, one with PPFIBP1, and one with ZCCHC8. DNA NGS analysis showed in five cases, specific mutations of AKT, EGFR, NRAS, MYC, ALK, and KIT. ROS1 lesions belonged predominantly to the 'atypical Spitz tumour' group, and showed mainly a nested histological pattern. Interestingly, one patient developed two ROS1-positive lesions. CONCLUSIONS Immunohistochemistry showed 100% sensitivity and specificity as compared with the FISH results, corresponding to ROS1 rearrangement in 31% of cases studied. These observations shed new light on the value of immunohistochemical evaluation of ROS1 in spitzoid tumours. ROS1 patterns of immunostaining probably reflect different subcellular localisations of ROS1 fusions, although no specific correlations were found in the cases studied. Immunohistochemistry and FISH were the most sensitive techniques for detecting ROS1 rearrangement in this subset of neoplasms.

Introduction: Based on the high incidence of thromboembolic events (TEs) observed in lung adenocarcinomas with ALK translocations and taking into account the biological proximity of ROS1 and ALK, we conducted a retrospective analysis of patients with advanced lung carcinoma carrying rearrangements in ROS1 from 23 centres in Spain and one centre in Portugal. Methods: The main objective of the study was to analyse the incidence of TE in this population, looking for predictive risk factors, and its impact on overall survival. Results: A total of 58 patients were included. The incidence of TEs throughout the disease was 46.6% (n = 27) with a median follow-up of 19 months (range: 1-78 months) and a median overall survival of 52 months in the total population and 50 months for the patients presenting TEs, with a hazards ratio of 1.12 (95% confidence interval: 0.47-2.65) p = 0.78. The majority of the events were venous (n = 24; 89%) and occurred in the ambulatory setting (n = 18; 67%). Almost half of the patients (n = 13; 48%) presented the TE in the peri-diagnostic period. Conclusions: The high incidence of thrombosis, especially during the cancer diagnosis process, requires special attention from a clinician. Despite the limitations of such a small descriptive study, its results are in accordance with previously reported data. It would be important to design prospective studies of antithrombotic prophylaxis in this population because of their possible impact in reducing the risk of TEs. (C) 2020 Elsevier Ltd. All rights reserved.

Carcinoma of unknown primary site (CUP) is diagnosed only in 2-9% of all cancer cases. Adenocarcinomas account for approximately 60% of CUP, and some of these are putative lung adenocarcinomas. The frequency of driver oncogene positivity in the putative lung adenocarcinomas is unknown, and the efficacy of targeting therapies for the driver oncogene is also unknown. This is the first case report of C-ros oncogene 1 (ROS1)-rearranged putative lung adenocarcinoma presenting as CUP showing a good response to ROS1 inhibitor therapy. A 55-year-old woman presented with neck lymphadenopathy. Computed tomography and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed swelling of the bilateral supraclavicular, left accessory, mediastinal, and abdominal lymph nodes. The pathological analysis of the lymph node specimen biopsy indicated adenocarcinoma with cytokeratin 7 and thyroid transcription factor-1 positivity. Thus, this case was identified as ROS1- rearranged putative lung adenocarcinoma presenting as CUP. Oral crizotinib, an ROS1 inhibitor, was administered at a dose of 250 mg twice daily. Four weeks later, several swollen nodes showed marked improvement, and eight weeks later, FDG PET showed almost no uptake. In conclusion, putative lung adenocarcinoma presenting as CUP may involve ROS1 rearrangement, and ROS1 inhibitor therapy may be effective.

ROS1 rearrangement occurs in 1–2% of non-small cell lung cancer (NSCLC) cases. These patients would benefit from treatment with the anaplastic lymphoma kinase inhibitor, crizotinib; however, resistance to crizotinib inevitably develops in such patients despite an initial response. The mechanism of acquired resistance to crizotinib in patients with NSCLC with ROS1 rearrangement has not yet been identified. Herein, we report a case of a 66-year-old woman diagnosed with adenocarcinoma. PCR revealed no EGFR or ALK mutations. After the patient underwent several rounds of chemotherapy, crizotinib was administered. The disease explosively progressed six months later. A novel PIK3CA gene point mutation (p.L531P) was detected by next generation sequencing. This case is the second report of bypass activation conferred crizotinib resistance in a patient with NSCLC with ROS1-rearrangement, but is the first to confirm that activation of the mTOR signaling pathway leads to acquired crizotinib resistance.

Background:Breast metastases from extramammary sites are extremely rare, with an incidence of 0.4%–1.3% reported in the literature. Insufficient knowledge about its pathology and genetic mutation often leads to misdiagnosis and delayed treatment.Case presentation:We present 2 patients with synchronous (case 1) or metachronous (case 2) breast nodules, revealed as atypical breast metastases from pulmonary adenocarcinomas, in which ALK or ROS1 rearrangement were finally detected in breast mass. After they failed sequential treatments with standard chemotherapies for lung and breast cancer, we reexamined breast lump biopsy and found they were all lung adenocarcinoma metastasis to the breast with the presence of an ALK rearrangement in one case and of ROS1 rearrangement in the other. Eventually these 2 patients were treated with crizotinib. Both the primary tumor and the metastasis of these 2 patients were significantly regressed.Conclusion:Whenever a diagnosis of a suspected tumor with sites at more than one organ is made, pathologic as well molecular pathologic examinations designated for organ-specific cancers should be done.

Background ROS1 rearrangements are validated drivers in lung cancer, which have been identified in a small subset (1–2%) of patients with non-small cell lung cancer (NSCLC). To date, 18 fusion genes of ROS1 have been identified in NSCLC. The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC. Next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers many fusion genes. Case presentation A 55-year-old female with EGFR mutation (L858R) was diagnosed with lung adenocarcinoma, who was responsive to first-generation EGFR-tyrosine kinase inhibitor (TKI). Afterwards, she developed acquired resistance accompanied with a ROS1 rearrangement. A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1–33 of ROS1 on chr6: q22.1 to exons of 2–26 of ADGRG6 on chr6: q24.2. The patient was obviously responsive to crizotinib. Conclusion We firstly identified ROS1-ADGRG6 fusion variant in NSCLC by NGS, which should be considered in further ROS1 detecting assays.

Purpose The recent discovery and characterization of an oncogenic ROS1 gene rearrangement has raised significant interest because small molecule inhibitors are effective in these tumors. The aim of this study was to determine frequency and clinicopathological features associated with ROS1 rearrangement in patients with cholangiocarcinoma (CCA). Materials and methods A total of 261 patients who underwent surgery for CCA between October 1997 and August 2013 were identified from an international, multi-institutional database. ROS1 rearrangement was evaluated by break-apart fluorescence in situ hybridization using tissue microarrays of these patients. Results Of 261 CCA evaluated, three cases (1.1%) showed ROS1 rearrangement by fluorescence in situ hybridization (FISH), all of which were derived from intrahepatic origin. ROS1 protein expression was observed in 38 samples (19.1%). Significantly larger tumor size was observed in ROS1 immunohistochemistry (IHC)-negative patients compared with ROS1 IHC-positive patients. ROS1 FISH-positive patients had a single tumor with a median size of 4 cm and well-to-moderate differentiation. Overall, there was no difference in terms of baseline characteristics, overall survival, and recurrence-free survival between ROS1-positive and -negative patients. Conclusion ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.

// Jing Zhao 1, * , Jing Zheng 2, * , Mei Kong 1 , Jianya Zhou 2 , Wei Ding 1 , Jianying Zhou 2 1 Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China 2 Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China * These authors have contributed equally to this work Correspondence to: Jing Zhao, email: 858585zhaojing@163.com Keywords: NSCLCs, ROS1 rearrangement, clinicopathological features, biopsy Received: May 30, 2016 Accepted: September 16, 2016 Published: September 30, 2016 ABSTRACT Defining distinctive histologic characteristics of ROS1 -rearranged non-small-cell lung carcinomas (NSCLCs) may help identify cases that merit molecular testing. However, the majority of previous reports have focused on surgical specimens but only limited studies assessed histomorphology of advanced NSCLCs. In order to identify the clinical and histological characteristics of ROS1 -rearranged advanced NSCLCs, we examined five hundred sixteen Chinese patients with advanced NSCLCs using ROS1 fluorescence in situ hybridization and real-time polymerase chain reaction and then analyzed for clinical and pathological features. We performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement. 19 tumors were identified with ROS1 rearrangement (3.7% of adenocarcinomas). 16 ROS1 + and 122 ROS1 - samples with available medical records and enough tumor cells were included for histological analysis. Compared with ROS1 -negative advanced NSCLCs, ROS1 -rearranged advanced NSCLCs were associated with a younger age at presentation. ROS1 rearrangements were not significantly associated with sex, smoking history, drinking history and metastatic sites. The most common histological pattern was solid growth (12/16), followed by acinar (4/16) growth. 66.7% cases with solid growth pattern showed hepatoid cytology (8/12) and 75% cases with acinar growth pattern showed a cribriform structure (3/4). 18.8% cases were found to have abundant extracellular mucus or signet-ring cells (3/16). Only one case with solid growth pattern showed psammomatous calcifications. In conclusion, age, hepatoid cytology and cribriform structure are the independent predictors for ROS1 -rearranged advanced NSCLCs, recognizing these may be helpful in finding candidates for genomic alterations, especially when available tissue samples are limited.

e21733 Background: ROS1 rearrangement occurs in approximately 1%-2% of non-small cell lung cancer, and it is predictive of treatment response to tyrosine kinase inhibitor. The gold standard method to detect ROS1 rearrangement is break-apart fluorescence in situ hybridization (FISH). ROS1 immunohistochemistry has been proposed as a cost-effective screening test for detection of ROS1 rearrangement. Most studies about the correlation between ROS1 FISH and immunohistochemistry derived from the D4D6 clone anti-ROS1 antibody. Recently, a novel anti-ROS1 antibody (SP384 clone) is available. However, data regarding the performance of this new anti-ROS1 antibody is still limited. In this study, we evaluated the performance of these two anti-ROS1 antibody as a screening tool to detect ROS1 rearrangement. Methods: Two hundred non-small cell lung cancers, including 18 ROS1 FISH-positive and 182 ROS1 FISH-negative samples, were studied. All specimens were stained with D4D6 clone and SP384 clone anti-ROS1 antibodies. The stained slides were scored by a pathologist using the H-score method, which was defined as the sum of products of multiplying intensity (0, 1, 2, and 3) by extent of each staining intensity (%). Receiver Operating Characteristics (ROC) curves were used to determine the optimal cut-off value that discriminates between ROS1-rearranged and non-rearranged tumors. Results: There was high correlation between the H-score of D4D6 clone and SP384 clone (Spearman's rho correlation coefficient = 0.862, P-value < 0.001). The SP384 clone showed a higher H-score than D4D6 clone (Wilcoxon signed rank test, P-value < 0.001). ROC analysis showed H-score of ≥ 150 was the optimal cut-off value for both D4D6 clone and SP384 clone to discriminate between ROS1-rearranged and non-rearranged tumors. Using this cut-off value, the D4D6 clone showed 100% sensitivity and 96.7% specificity; the SP384 clone showed 100% sensitivity and 95.1% specificity. The areas under ROC curve for D4D6 clone and SP384 clone were 0.992 and 0.990, respectively. Conclusions: The performance of D4D6 clone or SP384 clone is comparable. ROS1 IHC with either D4D6 clone or SP384 clone is a cost-effective screening tool for the presence of ROS1 rearrangements. [Table: see text]

It is widely known that ROS1 rearrangement mostly occurs in the adenocarcinoma subtype of non-small-cell lung cancer. Patients with squamous cell carcinoma harboring ROS1 rearrangement are extremely rare. This is a case report of a squamous cell carcinoma patient with ROS1 rearrangement. An 84-year-old Chinese woman with a about 6.6 cm mass in the right middle lobe and right pleural effusion, enlarged mediastinal and hilar lymph nodes was diagnosed with stage IIIB lung squamous cell carcinoma harboring ROS1 rearrangement is highly sensitive to crizotinib in the first treatment setting. This is the first time to report lung squamous carcinoma patient with ROS1 rearrangement sensitive to crizotinib. We hope that oncologists will notice this phenomenon and it will help the lung squamous cell carcinoma patient to get longer overall survival time.

Purpose: The aim of this study was to investigate the rate of ROS1 rearrangement and concordance between ROS1 immunohistochemistry (IHC) and molecular tests in non-small cell lung cancer (NSCLC). Methods: The study included 10,898 NSCLC cases from 21 eligible studies. ROS1 rearrangement rates were evaluated in NSCLC by a meta-analysis, including subgroup analyses. In addition, we performed a concordance analysis and a diagnostic test accuracy review of ROS1 IHC in NSCLC. Results: The estimated overall rate of ROS1 rearrangement and IHC positivity was 2.4% (95% confidence interval (CI) 1.5, 3.7). In the subgroup analysis, which was based on tumor subtype, the rate of ROS1 rearrangement and IHC positivity was 2.9% (95% CI 1.9, 4.5) and 0.6% (95% CI 0.3, 1.2) in adenocarcinoma and non-adenocarcinoma, respectively. The overall concordance rate between ROS1 IHC and molecular tests was 93.4% (95% CI 78.3, 98.2). In ROS1 IHC positive and negative cases, the concordance rates were 79.0% (95% CI 43.3, 94.9) and 97.0% (95% CI 83.3, 99.5), respectively. The pooled sensitivity and the specificity of ROS1 IHC were 0.90 (95% CI 0.70, 0.99) and 0.82 (95% CI 0.79, 0.84), respectively. The diagnostic odds ratio and the area under the curve of the summary receiver operating characteristic curve were 118.01 (95% CI 11.81, 1179.67) and 0.9417, respectively. Conclusion: The rates of ROS1 rearrangement differed by tumor histologic subtype in NSCLC. ROS1 IHC may be useful for the detection of ROS1 rearrangement in NSCLC. Detailed criteria for evaluating ROS1 IHC are needed before it can be applied in daily practice.

Background Crizotinib is recommended as first-line therapy in ROS1-driven lung adenocarcinoma. However, the optimal first-line therapy for this subgroup of lung cancer is controversial according to the available clinical data. Case presentation Here, we describe a 57-year-old man who was diagnosed with stage IIIB lung adenocarcinoma and EGFR/KRAS/ALK-negative tumors. The patient received six cycles of pemetrexed plus cisplatin as first-line therapy and then pemetrexed as maintenance treatment, with a progression-free survival (PFS) of 42 months. The patient relapsed and underwent re-biopsy. EZR-ROS1 fusion mutation was detected by next-generation sequencing (NGS). The patient was prescribed crizotinib as second-line therapy and achieved a PFS of 6 months. After disease progression, lorlatinib was administered as third-line therapy, with a favorable response. Conclusions Prolonged PFS in patients receiving pemetrexed chemotherapy might be related to the EZR-ROS1 fusion mutation. Lorlatinib is an optimal choice in patients showing crizotinib resistance.

The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor (EGFR) mutation or an anaplastic lymphoma kinase (ALK) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

Rational: The c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearrangements represent a new and rare genetic subtype of non-small-cell lung cancer. In recent years, the use of crizotinib in ROS1-rearranged lung cancer exhibits significant clinical efficacy. Crizotinib is generally well tolerated and the most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac, and endocrine abnormalities. From a cardiac perspective, crizotinib is associated with 2 main cardiac effects, QT interval prolongation and bradycardia. Patient concerns and diagnoses: We reported a case of a 67-year-old man with ROS1-rearranged advanced lung adenocarcinoma. Interventions: Crizotinib was initiated as first-line treatment, combined with whole brain radiation therapy. Outcomes: Interestingly, after treatment of crizotinib, the patient suffered a transient QTc interval prolongation and his persistent atrial fibrillation was changed into sinus bradycardia. Only 22 days after crizotinib treatment, the patient's tumor achieved a partial response. So far the patient has taken crizotinib for >19 months with no evidence of disease progression. Lessons: The present study demonstrates dramatic benefit of crizotinib for patients with ROS1 rearrangement. Besides, we should caution the cardiac effects caused by crizotinb and our case provides evidence that crizotinib may be safe for patients with atrial fibrillation under close monitoring.

9101 Background: ROS1 rearrangement is an important therapeutic target that occurs in approximately 1-2% of patients with non-small cell lung cancer (NSCLC). It has been shown that ROS1-rearranged patients could benefit from crizotinib treatment. However, the efficacy of crizotinib as compared with pemetrexed-based chemotherapy in such patients is unknown. Methods: Advanced ROS1-rearranged NSCLC patients receiving crizotinib or pemetrexed-based chemotherapy as first-line treatment in Shanghai Chest Hospital between August 2010 and December 2017 were retrospectively reviewed. Clinical characteristics, treatments and survival outcomes data were abstracted. Results: Of 77 patients included, 30 patients (39.0%) received crizotinib and 47 patients (61.0%) received pemetrexed-based chemotherapy as their first-line treatment. The median follow-up was 26.8 months. The objective response rate was significantly better with crizotinib than with pemetrexed-based therapy (86.7% vs 44.7%, P < 0.001). The disease control rate wasc 96.7% with crizotinib, as compared with 85.1% with pemetrexed-based therapy (P = 0.140). The median progression-free survival was significantly longer with crizotinib versus pemetrexed-based therapy (18.4 months [95% confidence interval [CI]: 6.8-30.0] vs 8.6 months [95% CI:7.1-10.2], P < 0.001). No significant difference in overall survival (OS) was observed between the two groups (Not reach vs 28.1 months [95% CI:18.7-38.5], P = 0.173). Six patients (20%) in the crizotinib group switched to pemetrexed-based therapy in subsequent lines, while twenty-nine patients (61.7%) in the chemotherapy group crossed over to receive crizotinib after progression. There was no significant difference in median OS between patients who received crizotinib first and those who received pemetrexed-based treatment prior to crizotinib (38.6 months [95% CI: 0-81.0] vs 32.7 months [95% CI:14.3-51.1], P = 0.890). Conclusions: Crizotinib is superior to pemetrexed-based chemotherapy as an initial treatment for advanced ROS1-rearranged NSCLC patients. The sequence of crizotinib treatment and pemetrexed-based chemotherapy does not influence OS.

Lancet Oncology, The - In Press.Proof corrected by the author Available online since mardi 7 novembre 2017

9067 Background: ROS1 rearrangement non–small-cell lung cancers can be effectively treated with ALK inhibitor such as crizotinib, but the response magnitude and duration are heterogeneous. Several ROS1 fusion partners have been identified, but few studies have focused on the effects of different fusion partners on the efficacy of crizotinib. Methods: Among 49 RT-PCR assay ROS1 rearrangement patients treated with crizotinib between April 2014 and November 2016, we identified 36 patients with tumor specimens that could be evaluated for the presence of different ROS1 fusion partners by Sanger sequencing. Patients continued crizotinib until RECIST-defined progression. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate(ORR), progression-free survival (PFS) and overall survival (OS) according to the different ROS1 fusion partners. Results: The most frequent ROS1 fusion partner was CD74-ROS1 (CD74-E6; ROS1-E34) in 16 patients (44.4%), followed by EZR-ROS1 (EZR-E10; ROS1-E34) in 7 patients (19.4%), SDC4 (SDC4-E2; ROS1-E32) in 4 patients (12%), SLC34A2-ROS1 (SLC34A2-E14del; ROS1-E32) in 2 patients (5.6%) and TPM3 (TPM3-E8; ROS1-E35) in 2 patients (5.6%). We also found that SDC4+EZR (SDC4-E2; ROS1-E32/EZR-E10; ROS1-E34) in 2 patients (5.6%), dual CD74-ROS1 (CD74-E6; ROS1-E32/34) in 2 patients (5.6%), CD74+SDC4 (SDC4-E2; ROS1-E32/CD74-E6; ROS1-E34) in 1 patient (2.8%). ORR was 83.3% in all patients, whereas it was 70.58% and 92.35% in the CD74 and non–CD74 groups, respectively (P = 0.17). The median PFS was longer in non–CD74 than in those with CD74 (median PFS, 17.67 months [95% CI, 12.14 to 23.19 ] vs 19.30 months [95% CI, not reached], respectively; P = 0.405) with no statistical significance. The median OS was significantly longer in patients with non–CD74 than in those with CD74 (median OS, 28.07 months [95% CI, 23.93 to 32.1] vs not reached, respectively; P = 0.043). Multivariable analysis identified 1 significant factor associated with OS, brain metastasis before crizotinib treatment (P < 0.001). Conclusions: Our results indicate the better OS of crizotinib in patients with non–CD74 vs CD74. The ROS1 fusion partnerS might affect the efficacy of ALK-TKIs.

e23086Background: Fluorescence in-situ hybridization (FISH) is the reference assay for ROS1 gene rearrangement. Molecular detection of ROS1 rearrangement in lung cancer has therapeutic relevance in...

e22203 Background: In this study, we aimed to identify incidence and clinicopathologic features of ROS1 rearrangement in LADC, cholangiocarcinoma (CCA) and glioblastoma multiforme (GBM), which were...

8066 Background: Rearrangements of the ROS1 oncogene occur in about 1-2% of non-small cell lung cancer (NSCLC) patients. While data suggest that the EML4-ALK/MET/ROS1 inhibitor crizotinib is highly...

e19003 Background: C-ros oncogene 1 receptor tyrosine kinase (ROS1) is a newly identified gene-rearranged oncogenic receptor tyrosine kinase and patients seem to benefit from crizotinib treatment. ...

2093 Background: The tirosine kinase (TK) receptor ROS1 is described in several preclinical analysis of glioblastoma (GBM) cells and its role in gliomagenesis has been reported as well. Since TK in...

Recent advances in molecular biology have led to the identification of new molecular targets for solid tumors, which were considered refractory to conventional cancer therapy, and efficacious molecular targeted drugs are being developed. For example, oncogenic drivers such as EGFR mutations, ALK rearrangement, ROS1 rearrangement, and RET rearrangement have been found in lung cancer, and dramatic therapeutic effects have been achieved with corresponding drugs in lung cancer expressing these driver oncogenes. On the other hand, patients who have responded to those inhibitors will acquire resistance within a few years and experience the recurrence of cancer, and several molecular targets for overcoming the resistance have also been identified. Using lung cancer as an example, new molecular targets will be introduced in this session.