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https://www.readbyqxmd.com/read/28529901/combining-immunotherapy-and-radiation-therapy-for-small-cell-lung-cancer-and-thymic-tumors
#1
REVIEW
Suchit H Patel, Andreas Rimner, Roger B Cohen
Recent work with immunotherapy has shown promising results with treatment of several solid malignancies, and there are several reports of good systemic responses with the combination of immunotherapy and radiation therapy (RT), most notably in advanced melanoma. Given the rapid increase in the use of checkpoint blockade as well as anti-tumor vaccines, we review here the preclinical rationale and ongoing clinical work in combining immunotherapy with RT for small cell lung cancer (SCLC) and thymic tumors. While there are several reports of promising results with the combination of immunotherapy and conventional systemic treatment, we focus here on the ongoing clinical studies that combine immunotherapy with RT, and highlight the emerging data for this multimodality approach as well as key preclinical and clinical issues that remain to be addressed...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529747/amrubicin-monotherapy-may-be-an-effective-second-line-treatment-for-patients-with-large-cell-neuroendocrine-carcinoma-or-high-grade-non-small-cell-neuroendocrine-carcinoma
#2
Norimitsu Kasahara, Kazushige Wakuda, Shota Omori, Kazuhisa Nakashima, Akira Ono, Tetsuhiko Taira, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Keita Mori, Reiko Watanabe, Masahiro Endo, Takashi Nakajima, Masanobu Yamada, Toshiaki Takahashi
There is no standard chemotherapy for pulmonary large-cell neuroendocrine carcinoma (LCNEC) and this type of cancer is difficult to diagnose using biopsy specimens. At the Shizuoka Cancer Center, when small biopsy specimens are used, they are diagnosed as high-grade non-small-cell neuroendocrine carcinoma (HNSCNEC) and the patients are treated according to the small-cell lung cancer (SCLC) guidelines. Amrubicin is an effective second-line treatment for patients with SCLC, although it remains unclear whether amrubicin monotherapy is effective for patients with LCNEC or HNSCNEC...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28529640/lung-cancer-targeting-peptides-with-multi-subtype-indication-for-combinational-drug-delivery-and-molecular-imaging
#3
Yi-Hsuan Chi, Jong-Kai Hsiao, Ming-Huang Lin, Chen Chang, Chun-Hsin Lan, Han-Chung Wu
Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (LCC) or small cell lung cancer (SCLC). Therefore, we aimed to identify targeting peptides with diagnostic and therapeutic utility that possess broad subtype specificity for SCLC and non-small cell lung cancer (NSCLC)...
2017: Theranostics
https://www.readbyqxmd.com/read/28526735/activated-notch-induced-intratumoral-heterogeneity-drives-lung-cancer
#4
(no author information available yet)
Activated NOTCH signaling is both tumor-suppressive and protumorigenic in SCLC.
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28526406/trastuzumab-emtansine-suppresses-the-growth-of-her2-positive-small-cell-lung-cancer-in-preclinical-models
#5
Osamu Morimura, Toshiyuki Minami, Takashi Kijima, Shohei Koyama, Tomoyuki Otsuka, Yuhei Kinehara, Akio Osa, Masayoshi Higashiguchi, Kotaro Miyake, Izumi Nagatomo, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
Overcoming chemoresistance is essential for achieving better prognoses in SCLC. Previously, we reported that HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance. HER2-upregulated cisplatin- or etoposide-resistant SCLC cells were sensitive to trastuzumab-mediated ADCC. However, irinotecan-resistant SCLC cells, such as SBC-3/SN-38, were refractory to trastuzumab despite high HER2 expression. To address this issue, we examined the antitumor efficacy of trastuzumab emtansine (T-DM1) on trastuzumab-resistant HER2-positive SCLC...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28521472/cd117-expression-is-a-predictive-marker-for-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#6
Tomohiko Sakabe, Junya Azumi, Tomohiro Haruki, Yoshihisa Umekita, Hiroshige Nakamura, Goshi Shiota
Non-small cell lung cancer (NSCLC) accounts for >85% of incidences of lung cancer, for which the predicted 5-year survival rates are low and recurrence rates remain high. Although it has been reported that the patients with SCLC cells that possess the cluster of differentiation (CD) 117 marker exhibited poor prognosis and poor response to chemotherapy, no studies concerning the association of CD117 expression with prognosis of the patients with NSCLC have been reported. An in vitro study reportedly revealed that CD117-positive cell populations in NSCLC cell lines exhibited cancer stem cell (CSC) phenotypes including self-renewal and chemoresistance...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521295/change-from-lung-adenocarcinoma-to-small-cell-lung-cancer-as-a-mechanism-of-resistance-to-afatinib
#7
Paolo Manca, Marco Russano, Francesco Pantano, Giuseppe Tonini, Daniele Santini
We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma. Unexpectedly, the switch to SCLC histotype occurred in the only site not responsive to afatinib and subsequently the most responsive to chemotherapy. Our case shows that occurrence of switch to SCLC is a possible mechanism of resistance during treatment with Afatinib...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516335/prognostic-value-of-pre-treatment-18-f-fdg-pet-uptake-in-small-cell-lung-cancer
#8
Meryem Aktan, Mehmet Koc, Gul Kanyilmaz, Berrin Benli Yavuz
PURPOSE: Small-cell lung cancer (SCLC) is an aggressive disease, despite an initially favorable response to treatment, and its prognosis is still poor. Multiple parameters have been studied as possible prognostic factors, but none of them are reliable enough to change the treatment approach. (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is a novel imaging technique for staging of SCLC. The aim of this study was to evaluate the prognostic value of pre-treatment FDG-PET parameters on clinical outcome in limited stage (LS) SCLC patients treated with curative thoracic radiotherapy (RT) and chemotherapy...
May 17, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28512410/rrx-001-priming-of-pd-1-inhibition-in-the-treatment-of-small-cell-carcinoma-of-the-vagina-a-rare-gynecological-tumor
#9
Christina Brzezniak, Bryan Oronsky, Jane Trepel, Thomas A Summers, Pedro Cabrales, Min-Jung Lee, Regina Day, Saheli Jha, Scott Caroen, Karen Zeman, Lindsey Ferry, Cindy Harmer, Neil Oronsky, Michelle Lybeck, Harry E Lybeck, James F Brown, Tony R Reid, Corey A Carter
Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant) and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28510571/second-line-pazopanib-in-patients-with-relapsed-and-refractory-small-cell-lung-cancer-a-multicentre-phase-ii-study-of-the-hellenic-oncology-research-group
#10
F Koinis, S Agelaki, V Karavassilis, N Kentepozidis, E Samantas, S Peroukidis, P Katsaounis, E Hartabilas, I I Varthalitis, I Messaritakis, G Fountzilas, V Georgoulias, A Kotsakis
BACKGROUND: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. PATIENTS AND METHODS: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort...
May 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28508473/vertical-charge-transport-via-small-polaron-hopping-within-tips-pentacene-lamellar-single-crystal
#11
Jiawei Wang, Tianjun Liu, Ji Dong, Molin Li, Jun He, Chao Jiang
A modified liquid method is employed to grow an ultralarge 6,13-bis(triisopropylsilylethynyl)pentacene crystal, ensuring fabrication and measurements of the two terminal devices. The hole transport mechanism is studied by analyzing the space charge limited currents (SCLCs) at various temperatures. Modified SCLC theory with a small polaron hopping model is developed and employed to successfully simulate the I-V curves. Values of effective hopping distance, transfer integral, and reorganization energy are extracted and reasonably discussed...
May 16, 2017: Small
https://www.readbyqxmd.com/read/28502129/diagnostic-role-of-rassf1a-and-p16ink4a-promoter-gene-hypermethylation-in-serum-dna-of-lung-cancer-patients-clinicopathological-significance
#12
Wafaa T El-Sherif, Sohair K Sayed, Sherif H Galal, Hoda A Makhlouf, Alaa T Hassan, Hosam A Yousef
The most common inactivation mechanism of tumor suppressor genes, RASSF1A and p16INK4a, in lung cancer is hypermethylation. We detected the methylation status of RASSF1A and p16INK4a in serum of lung cancer patients using methylation-specific PCR and analyzed their clinicopathological significance. Each of RASSF1A and p16INK4a hypermethylation was detected in 31.1% cancer patients but not in benign lung lesion patients. Hypermethylation was preferentially observed in small cell lung cancer (SCLC) for RASSF1A (50%), but not for p16INK4a...
June 2016: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/28498782/clonal-history-and-genetic-predictors-of-transformation-into-small-cell-carcinomas-from-lung-adenocarcinomas
#13
June-Koo Lee, Junehawk Lee, Sehui Kim, Soyeon Kim, Jeonghwan Youk, Seongyeol Park, Yohan An, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Young Tae Kim, Jin-Soo Kim, Se Hyun Kim, Jong Seok Lee, Se-Hoon Lee, Keunchil Park, Ja-Lok Ku, Yoon Kyung Jeon, Doo Hyun Chung, Peter J Park, Joon Kim, Tae Min Kim, Young Seok Ju
Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at various time points from four patients to reconstruct their clonal evolutionary history and to detect genetic predictors for small-cell transformation...
May 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28490518/chk1-inhibition-in-small-cell-lung-cancer-produces-single-agent-activity-in-biomarker-defined-disease-subsets-and-combination-activity-with-cisplatin-or-olaparib
#14
Triparna Sen, Pan Tong, C Allison Stewart, Sandra Cristea, Aly Valliani, David S Shames, Abena Redwood, Youhong Fan, Lerong Li, Bonnie S Glisson, John Minna, Julien Sage, Don L Gibbons, Helen Piwnica-Worms, John Heymach, Jing Wang, Lauren Averett Byers
Effective targeted therapies for small cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacological blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models...
May 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28488812/decreased-body-mass-index-is-associated-with-impaired-survival-in-lung-cancer-patients-with-brain-metastases-a-retrospective-analysis-of-624-patients
#15
E K Masel, A S Berghoff, L M Füreder, P Heicappell, F Schlieter, G Widhalm, B Gatterbauer, U Dieckmann, P Birner, R Bartsch, S Schur, H H Watzke, C C Zielinski, M Preusser
Body mass index (BMI) is a prognostic factor in several cancer types. We investigated the prognostic role of BMI in a large patient cohort with newly diagnosed lung cancer brain metastases (BM) between 1990 and 2013. BMI at diagnosis of BM and graded prognostic assessment (GPA) were calculated. Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50-24.99) and overweight (BMI ≥ 25.00). A total of 624 patients (men 401/624 [64.3%]; women 223/624 [35.7%]; median age of 61 [range 33-88]) were analysed...
May 10, 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28487384/non-invasive-interrogation-of-dll3-expression-in-metastatic-small-cell-lung-cancer
#16
Sai Kiran Sharma, Jacob Pourat, Dalya Abdel-Atti, Sean D Carlin, Alessandra Piersigilli, Alexander J Bankovich, Eric E Gardner, Omar Hamdy, Kumiko Isse, Sheila Bheddah, Joseph Sandoval, Kristen M Cunanan, Eric B Johansen, Viola Allaj, Vikram Sisodiya, David Liu, Brian M Zeglis, Charles M Rudin, Scott J Dylla, J T Poirier, Jason S Lewis
The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T™; SC16LD6.5) is a first-in-class DLL3-targeted antibody-drug conjugate with encouraging initial safety and efficacy profiles in SCLC in the clinic. Here we demonstrate that tumor expression of DLL3, though orders of magnitude lower in surface protein expression than typical oncology targets of immunoPET, can serve as an imaging biomarker for SCLC...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28482670/immune-checkpoint-inhibitors-in-lung-cancer-current-status-and-future-directions
#17
Yun Fan, Weimin Mao
Recently, the immune checkpoint inhibitors that target programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) have made a breakthrough in treating advanced non-small cell lung cancer (NSCLC) with the efficacy of approximately 20%; among which, nivolumab has acquired treatment indications in lung squamous cell carcinoma. The inhibitors targeting cytotoxic T lymphocyte associated antigen 4 (CTLA-4) are also undergoing clinical trials. Researches on immune checkpoint inhibitors have been rapidly implemented in a variety of different types of lung cancer, such as small cell lung cancer (SCLC) and locally advanced NSCLC, and these inhibitors began to be applied in combination with some established treatments, including chemotherapy, targeting therapy and radiotherapy...
April 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28475559/long-term-survival-after-surgery-compared-with-concurrent-chemoradiation-for-node-negative-small-cell-lung-cancer
#18
Chi-Fu Jeffrey Yang, Derek Y Chan, Shivani A Shah, Babatunde A Yerokun, Xiaofei F Wang, Thomas A D'Amico, Mark F Berry, David H Harpole
OBJECTIVE: To determine whether surgery with adjuvant chemotherapy offers a survival advantage over concurrent chemoradiation for patients with cT1-2N0M0 small cell lung cancer (SCLC). BACKGROUND: Although surgery with adjuvant chemotherapy is the recommended treatment for patients with cT1-2N0M0 SCLC per international guidelines, there have been no prospective or retrospective studies evaluating the impact of surgery versus optimal medical management for cT1-2N0M0 SCLC...
May 4, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28474864/the-impact-of-met-inhibition-on-small-cell-lung-cancer-cells-exhibiting-aberrant-activation-of-the-hgf-met-pathway
#19
Hirokazu Taniguchi, Tadaaki Yamada, Shinji Takeuchi, Sachiko Arai, Koji Fukuda, Shuichi Sakamoto, Manabu Kawada, Hiroyuki Yamaguchi, Hiroshi Mukae, Seiji Yano
Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers, and is characterized as being extremely aggressive, often displaying rapid tumor growth and multiple organ metastases. In addition, the clinical outcome of SCLC patients is poor due to early relapse and acquired resistance to standard chemotherapy treatments. Hence, novel therapeutic strategies for the treatment of SCLC are urgently required. Accordingly, several molecular targeted therapies were evaluated in SCLC; however, they failed to improve the clinical outcome...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28468776/vulnerability-of-small-cell-lung-cancer-to-apoptosis-induced-by-the-combination-of-bet-bromodomain-proteins-and-bcl2-inhibitors
#20
Lloyd T Lam, Xiaoyu Lin, Emily J Faivre, Ziping Yang, Xiaoli Huang, Denise M Wilcox, Richard J Bellin, Sha Jin, Stephen K Tahir, Michael Mitten, Terry Magoc, Anahita Bhathena, Warren M Kati, Daniel H Albert, Yu Shen, Tamar Uziel
10% to 15% of all lung cancers are small cell lung cancer (SCLC). SCLC usually grows and metastasizes before it is diagnosed and relapses rapidly upon treatment. Unfortunately, no new targeted agent has been approved in the past 30 years for patients with SCLC. The BET (bromodomain and extra-terminal) proteins bind acetylated histones and recruit protein complexes to promote transcription initiation and elongation. BET proteins have been shown to regulate expression of key genes in oncogenesis such as MYC, CCND2, and BCL2L1 Here, we demonstrate that ~50% of SCLC cell lines are exquisitely sensitive to growth inhibition by the BET inhibitor, ABBV-075...
May 3, 2017: Molecular Cancer Therapeutics
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