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https://www.readbyqxmd.com/read/29915896/targeting-egfr-in-lung-cancer-current-standards-and-developments
#1
REVIEW
Asunción Díaz-Serrano, Pablo Gella, Elisabeth Jiménez, Jon Zugazagoitia, Luis Paz-Ares Rodríguez
Lung cancer is the second most common malignant tumor and the leading cause of cancer death. Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a distinct subtype of lung cancer comprising approximately 15-40% of non-squamous tumors. The development of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) has been a significant step forward in the treatment of patients with EGFR-mutant tumors, and over the last few years has been the therapy of choice in the initial management of patients with activating mutations in EGFR, with some differences in efficacy and toxicity profile...
June 18, 2018: Drugs
https://www.readbyqxmd.com/read/29911108/emerging-application-of-genomics-guided-therapeutics-in-personalized-lung-cancer-treatment
#2
REVIEW
Aubhishek Zaman, Trever G Bivona
In lung cancer, genomics-driven comprehensive molecular profiling has identified novel chemically and immunologically addressable vulnerabilities, resulting in an increasing application of precision medicine by targeted inactivation of tumor oncogenes and immunogenic activation of host anti-tumor surveillance as modes of treatment. However, initially profound response of these targeted therapies is followed by relapse due to therapy-resistant residual disease states. Although distinct mechanisms and frameworks for therapy resistance have been proposed, accounting for and upfront prediction of resistance trajectories has been challenging...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29909991/overcoming-resistance-to-targeted-anticancer-therapies-through-small-molecule-mediated-mek-degradation
#3
Jessie Peh, Matthew W Boudreau, Hannah M Smith, Paul J Hergenrother
The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Here we demonstrate a general strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL)...
May 18, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29890761/current-and-future-molecular-testing-in-nsclc-what-can-we-expect-from-new-sequencing-technologies
#4
REVIEW
Simon Garinet, Pierre Laurent-Puig, Hélène Blons, Jean-Baptiste Oudart
Recent changes in lung cancer care, including new approvals in first line and the introduction of high-throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article, we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies...
June 9, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29881714/mechanisms-and-therapy-for-cancer-metastasis-to-the-brain
#5
REVIEW
Federica Franchino, Roberta Rudà, Riccardo Soffietti
Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs). Intracranial metastases are symptomatic in 60-70% of patients. Magnetic resonance imaging (MRI) with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29862231/beyond-egfr-and-alk-targeting-rare-mutations-in-advanced-non-small-cell-lung-cancer
#6
REVIEW
Stavros Gkolfinopoulos, Giannis Mountzios
Lung cancer remains the leading cause of cancer-related death in men and women, despite its constantly declining rates in incidence and mortality in the developed world. The past decade has witnessed an unprecedented rise in the development of molecular targeted therapies in various types of tumors. In non-small cell lung cancer (NSCLC), the greatest paradigm shift is the implementation of EGFR and ALK tyrosine kinase inhibitors in the first line and subsequent lines of therapy, with impressive results. Though less frequent than the molecular alterations in the aforementioned genes, a number of aberrations in potential oncogenic drivers has been discovered, namely mutations in the genes KRAS , BRAF , HER2 , PI3KCA and DDR2 , ROS1 and RET rearrangements and MET , HER2 and FGFR1 gene amplifications...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29852147/pericardial-and-pleural-metastases-clinical-histological-and-molecular-differences
#7
Georgia Karpathiou, Mousa Mobarki, Marie Laure Stachowicz, Sirine Hathroubi, Arnaud Patoir, Olivier Tiffet, Marios Froudarakis, Michel Peoc'h
BACKGROUND: Pericardial and pleural cavities produce effusions with important clinical consequences. Metastases are one of the most common etiologies of both serosal effusions. However, data regarding the type of metastatic involvement of the pleura and the pericardium are lacking. The aim of the study is to investigate the histological patterns of tumors involving the two cavities in order to better define their pathophysiology and possible consequences in molecular diagnostics. METHODS: This is a retrospective study of patients diagnosed with pericardial (n=75) and pleural (n=70) metastases...
May 28, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29850361/braf-inhibitors-for-braf-v600e-mutant-colorectal-cancers-literature-survey-and-case-report
#8
Yasar Subutay Peker, Mehmet Fatih Can, Ismail Hakki Ozerhan, Gokhan Yagci, Nazif Zeybek, Kutan Kavakli, Sedat Gurkok, Alper Gozubuyuk, Onur Genc, Gokhan Erdem, Ahmet Ozet, Mustafa Gerek, Yusuf Peker
The main method of fighting against colon cancer is targeted treatment. BRAF inhibitors, which are accepted as standard treatment for V600E mutant malign melanomas, are the newest approach for targeted treatment of V600E mutant colorectal cancers. In this case report, we share our experience about the use of BRAF inhibitor vemurafenib on a V600E mutant metastatic right colon adenocarcinoma patient. A 59-year-old male with only lung multiple metastatic V600E mutant right colon cancer presented to our clinic...
2018: Case Reports in Surgery
https://www.readbyqxmd.com/read/29846186/bronchiolar-adenoma-expansion-of-the-concept-of-ciliated-muconodular-papillary-tumors-with-proposal-for-revised-terminology-based-on-morphologic-immunophenotypic-and-genomic-analysis-of-25-cases
#9
Jason C Chang, Joseph Montecalvo, Laetitia Borsu, Shaohua Lu, Brandon T Larsen, William Dean Wallace, Wichit Sae-Ow, Alexander C Mackinnon, Hyunjae R Kim, Anita Bowman, Jennifer L Sauter, Maria E Arcila, Marc Ladanyi, William D Travis, Natasha Rekhtman
We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer of basal cells. These lesions shared some histologic features with the recently described entity of ciliated muconodular papillary tumor (CMPT); however, the majority did not fit all diagnostic criteria in that they exhibited only focal or absent papillary architecture, and they had variable number of ciliated and mucinous cells, with some lesions entirely lacking 1 or both of these components...
May 24, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29808006/shp2-is-required-for-growth-of-kras-mutant-non-small-cell-lung-cancer-in-vivo
#10
Sara Mainardi, Antonio Mulero-Sánchez, Anirudh Prahallad, Giovanni Germano, Astrid Bosma, Paul Krimpenfort, Cor Lieftink, Jeffrey D Steinberg, Niels de Wit, Samuel Gonçalves-Ribeiro, Ernest Nadal, Alberto Bardelli, Alberto Villanueva, Rene Bernards
RAS mutations are frequent in human cancer, especially in pancreatic, colorectal and non-small-cell lung cancers (NSCLCs)1-3 . Inhibition of the RAS oncoproteins has proven difficult 4 , and attempts to target downstream effectors5-7 have been hampered by the activation of compensatory resistance mechanisms 8 . It is also well established that KRAS-mutant tumors are insensitive to inhibition of upstream growth factor receptor signaling. Thus, epidermal growth factor receptor antibody therapy is only effective in KRAS wild-type colon cancers9,10 ...
May 28, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29788737/diagnosis-for-carcinoma-of-unknown-primary-site-with-the-aid-of-simple-pcr-tests-a-single-center-experience
#11
E Suspitsin, G Yanus, E Imyanitov
This study was aimed to incorporate PCR testing in the determination of organ/tissue origin for cancers of unknown primary site (CUP). We developed a PCR panel consisting of 7 expression markers (CDX2, CDH17, SPB, UGRP, MAM, LPB, TG) and 2 genes frequently mutated in cancer (KRAS and BRAF). The expression tests were intentionally interpreted in a non-quantitative way, i.e. classified tumors either as positive or negative expressors. While applying these tests to 135 cancers belonging to 8 common types of adenocarcinomas (AdCa), we observed that this panel was capable to clearly discriminate between gastrointestinal vs...
March 14, 2018: Neoplasma
https://www.readbyqxmd.com/read/29784736/targeted-therapy-for-patients-with-metastatic-non-small-cell-lung-cancer
#12
Karen L Reckamp
Molecular testing is recommended for initial diagnosis in patients with non-small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging "actionable" targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29772692/insurance-coverage-policies-for-pharmacogenomic-and-multi-gene-testing-for-cancer
#13
Christine Y Lu, Stephanie Loomer, Rachel Ceccarelli, Kathleen M Mazor, James Sabin, Ellen Wright Clayton, Geoffrey S Ginsburg, Ann Chen Wu
Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR ) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests...
May 16, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29769567/genomic-alterations-of-ground-glass-nodular-lung-adenocarcinoma
#14
Hyun Lee, Je-Gun Joung, Hyun-Tae Shin, Duk-Hwan Kim, Yujin Kim, Hojoong Kim, O Jung Kwon, Young Mog Shim, Ho Yun Lee, Kyung Soo Lee, Yoon-La Choi, Woong-Yang Park, D Neil Hayes, Sang-Won Um
In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29764505/xenograft-tumors-derived-from-malignant-pleural-effusion-of-the-patients-with-non-small-cell-lung-cancer-as-models-to-explore-drug-resistance
#15
Yunhua Xu, Feifei Zhang, Xiaoqing Pan, Guan Wang, Lei Zhu, Jie Zhang, Danyi Wen, Shun Lu
BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively...
May 9, 2018: Cancer communications
https://www.readbyqxmd.com/read/29760834/a-case-series-of-two-patients-presenting-with-pericardial-effusion-as-first-manifestation-of-non-small-cell-lung-cancer-with-braf-mutation-and-expression-of-pd-l1
#16
Muhammad Mufti, Steven Ching, Sassan Farjami, Sharareh Shahangian, Serap Sobnosky
Lung cancer is the number one cause of cancer-related deaths in the United States. Involvement of pericardium occurs once cancer has progressed to stage IV which can cause massive effusion in the pericardial sac. This can lead to cardiac tamponade which can be fatal very quickly if untreated. The following is a two patient case series in which both patients presented with large pericardial effusion. The first patient sought medical attention due to new onset palpitations and was found to have hemorrhagic pericardial effusion and pulmonary embolism (PE)...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29755687/clinical-application-of-targeted-next-generation-sequencing-for-colorectal-cancer-patients-a-multicentric-belgian-experience
#17
Nicky D'Haene, Quitterie Fontanges, Nancy De Nève, Oriane Blanchard, Barbara Melendez, Monique Delos, Marie-Françoise Dehou, Calliope Maris, Nathalie Nagy, Emmanuel Rousseau, Josse Vandenhove, André Gilles, Carine De Prez, Laurine Verset, Marie-Paule Van Craynest, Pieter Demetter, Jean-Luc Van Laethem, Isabelle Salmon, Marie Le Mercier
International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#18
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29748372/traf1-is-critical-for-regulating-the-braf-mek-erk-pathway-in-non-small-cell-lung-carcinogenesis
#19
Qiushi Wang, Ge Gao, Tianshun Zhang, Ke Yao, Hanyong Chen, Mi Hee Park, Hiroyuki Yamamoto, Keke Wang, Weiya Ma, Margarita Malakhova, Ann M Bode, Zigang Dong
Tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) is a unique TRAF protein that can interact directly or indirectly with multiple TNFR family members, regulatory proteins, kinases, and adaptors that contribute to its diverse functions in specific tissues. However, the role of TRAF1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we report that TRAF1 is overexpressed in human lung cancer cells and tissues. TRAF1 expression level inversely correlated with patient survival probability...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29736852/thoracic-involvement-in-erdheim-chester-disease-computed-tomography-imaging-findings-and-their-association-with-the-braf-v600e-mutation
#20
S Mojdeh Mirmomen, Arlene Sirajuddin, Moozhan Nikpanah, Rolf Symons, Anna K Paschall, Ioannis Papageorgiou, William A Gahl, Kevin O'Brien, Juvianee I Estrada-Veras, Ashkan A Malayeri
OBJECTIVES: To investigate the computed tomography (CT) thoracic findings in Erdheim-Chester disease (ECD) and evaluate the association of these findings with the BRAFV600E mutation. METHODS: This was a prospective study of patients with ECD (n=61, men=46) who underwent thoracic CT imaging. CT examinations were independently interpreted by two experienced radiologists. Association of imaging findings with BRAFV600E was achieved via the Chi-square or Fisher's exact test and odds ratios (OR) with 95% confidence intervals (CI), as appropriate...
May 7, 2018: European Radiology
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