Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

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Cancer Genome Landscapes

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

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The cancer genome atlas pan-cancer analysis project

The Cancer Genome Atlas Pan-Cancer analysis project

Background Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non–small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase. Methods After screening tumor samples from approximately 1500 patients with non–small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy. Results Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects. Conclusions The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)

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Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer

https://www.hal.inserm.fr/inserm-00561753/document

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

A 71-year-old man who had undergone surgery for stage II adenocarcinoma of the lung followed by adjuvant tegafur-uracil (UFT®; 300 mg/day) therapy was admitted. Multiple nodules were found in both lungs on chest radiographs obtained 1.5 years after the surgery. Imaging characteristics of the nodules resembled those of pulmonary metastases. Histologic assessment of a biopsy specimen obtained during thoracoscopic resection revealed pulmonary cryptococcosis. The patient was administered 200 mg/day fluconazole for 6 months. Physicians need to be aware of the possibility of pulmonary cryptococcosis mimicking pulmonary metastases in patients treated with UFT® after surgery for lung cancer.

Pulmonary cryptococcosis mimicking pulmonary metastases in a patient treated with Tegafur-uracil after lung cancer surgery.

Endoscope-assisted superior septal approach for resection of left atrial myxoma.

Postoperative studies in patients with stage III and IV lung cancer

症例は55歳, 男性.咳嗽と発熱を主訴に入院. 胸部X線写真にて左側胸水を認め, 炎症反応高値, 胸水検査では好中球が97%より, 膿胸を考えた. 抗生剤投与, 胸腔ドレナージを開始したが改善がみられず, 外科的に左胸膜剥皮術を施行した.術後病理組織では悪性胸膜中皮腫, 肉腫型と診断された. 悪性胸膜中皮腫では発熱, 炎症反応高値を伴うものもあり, 胸膜の肥厚を伴う膿胸などとの鑑別を慎重に行う必要があるものと考えられた.

A Case of Malignant Mesothelioma Similar to Empyema in Clinical Symptoms.

Repeat median sternotomy does not allow good access for retrosternal re-entry. Conversely, by using the plastron-trapdoor technique, which we describe in this report, the retrosternal tissues are dissected from the body of the sternum under direct vision, thus allowing relatively safe and wide exposure for retrosternal re-entry.

Yasunori Sohara

Papers

Pulmonary cryptococcosis mimicking pulmonary metastases in a patient treated with Tegafur-uracil after lung cancer surgery.

Endoscope-assisted superior septal approach for resection of left atrial myxoma.

Postoperative studies in patients with stage III and IV lung cancer

A Case of Malignant Mesothelioma Similar to Empyema in Clinical Symptoms.

Plastron-trapdoor technique for direct-vision sternal re-entry.