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Therapeutic Advances in Medical Oncology

Jessica Yang, Daniel K Manson, Brian P Marr, Richard D Carvajal
Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting...
2018: Therapeutic Advances in Medical Oncology
Arduino A Mangoni, Ganessan Kichenadasse, Andrew Rowland, Michael J Sorich
Background: There is inconsistency in the criteria used to define anti-vascular endothelial growth factor (VEGF) drug-induced hypertension (AVEGF-HT) in published studies. It is unknown whether specific patient characteristics similarly predict AVEGF-HT using different criteria. Methods: We assessed the associations between clinical and demographic factors (n = 22) and AVEGF-HT, using six criteria based on predefined on-treatment blood pressure (BP) thresholds or absolute BP elevations versus baseline, in a post hoc analysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study)...
2018: Therapeutic Advances in Medical Oncology
Zubair Ahmed Ratan, Young-Jin Son, Mohammad Faisal Haidere, Bhuiyan Mohammad Mahtab Uddin, Md Abdullah Yusuf, Sojib Bin Zaman, Jong-Hoon Kim, Laila Anjuman Banu, Jae Youl Cho
Bacteria and archaea possess adaptive immunity against foreign genetic materials through clustered regularly interspaced short palindromic repeat (CRISPR) systems. The discovery of this intriguing bacterial system heralded a revolutionary change in the field of medical science. The CRISPR and CRISPR-associated protein 9 (Cas9) based molecular mechanism has been applied to genome editing. This CRISPR-Cas9 technique is now able to mediate precise genetic corrections or disruptions in in vitro and in vivo environments...
2018: Therapeutic Advances in Medical Oncology
Szu-Chun Yang, Chien-Chung Lin, Wu-Wei Lai, Sheng-Mao Chang, Jing-Shiang Hwang, Wu-Chou Su, Jung-Der Wang
Background: Three different tyrosine kinase inhibitors have been approved as first-line therapies for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with similar overall survival. This study determined dynamic changes in quality of life (QoL) for patients using these therapies after controlling for potential confounders. Methods: From 2011 to 2016, we prospectively assessed the utility values and QoL scores of patients using the EuroQol five-dimension and World Health Organization Quality-of-Life - Brief questionnaires...
2018: Therapeutic Advances in Medical Oncology
Yan Wu, Miaomiao Yuan, Wenbin Su, Miaolin Zhu, Xiaoyuan Yao, Ying Wang, Hai Qian, Lu Jiang, Yan Tao, Min Wu, Ji Pang, Yongchang Chen
Type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) is a membrane-anchored enzyme expressed mainly in the intestinal mucosa and the brain, and is associated with various physiological or pathological processes. Upregulation of PKG II is known to induce apoptosis and inhibit proliferation and metastasis of cancer cells. The inhibitory effect of PKG II has been shown to be dependent on the inhibition of the activation of epidermal growth factor receptor (EGFR) and blockade of EGFR downstream signal transduction in vitro...
2018: Therapeutic Advances in Medical Oncology
Laurence Faugeras, Anne-Sophie Pirson, Julian Donckier, Luc Michel, Julien Lemaire, Sebastien Vandervorst, Lionel D'Hondt
The incidence of thyroid cancer has increased markedly in recent decades, but has been stable in terms of mortality rates. For the most part, these cancers are treated with surgery, which may or may not be followed by radioactive iodine depending on the tumor subtype. Still, many of these cancers will recur and may be treated with radioactive iodine or another surgery. It is unclear what treatment is best for cases of locally advanced or metastatic thyroid cancer that are refractory to radioactive iodine. Chemotherapy has a very low response rate...
2018: Therapeutic Advances in Medical Oncology
Vera Hirsh
Four epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib and osimertinib, are currently available for the management of EGFR mutation-positive non-small-cell lung cancer (NSCLC), with others in development. Although tumors are exquisitely sensitive to these agents, acquired resistance is inevitable. Furthermore, emerging data indicate that first- (erlotinib and gefitinib), second- (afatinib) and third-generation (osimertinib) EGFR TKIs differ in terms of efficacy and tolerability profiles...
2018: Therapeutic Advances in Medical Oncology
Jun Zhu, Feng Tang, Ye Gu
Background: It is difficult to collect peripheral lung cancer samples. This study analyzed the applicability of endobronchial ultrasonography with a guide sheath (EBUS-GS) and computed tomography-guided transthoracic needle aspiration (CT-TTNA) for the diagnosis of peripheral lung cancer. Methods: A prospective analysis of peripheral lung cancer patients was performed. The study included 150 cases in the EBUS-GS group and 177 cases in the CT-TTNA group. The diagnostic rate, pathological type, genetic status and complications were analyzed...
2018: Therapeutic Advances in Medical Oncology
John Shen, Jason Chang, Melody Mendenhall, Grace Cherry, Jonathan W Goldman, Rajan P Kulkarni
Background: The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management...
2018: Therapeutic Advances in Medical Oncology
Galatea Kallergi, Eleni-Kyriaki Vetsika, Despoina Aggouraki, Eleni Lagoudaki, Anastasios Koutsopoulos, Filippos Koinis, Panagiotis Katsarlinos, Maria Trypaki, Ippokratis Messaritakis, Christos Stournaras, Vassilis Georgoulias, Athanasios Kotsakis
Background: Circulating tumor cells (CTCs) could escape from the immune system through the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis leading to the development of metastasis. The current study investigated the expression of PD-1/PD-L1 on CTCs isolated from non-small cell lung cancer (NSCLC) patients treated with chemotherapy. Patients and methods: CTCs were isolated from 30 chemo-naïve stage IV NSCLC patients before and after front-line chemotherapy using the ISET filtration platform...
2018: Therapeutic Advances in Medical Oncology
Niki Karachaliou, Maria Gonzalez-Cao, Guillermo Crespo, Ana Drozdowskyj, Erika Aldeguer, Ana Gimenez-Capitan, Cristina Teixido, Miguel Angel Molina-Vila, Santiago Viteri, Maria De Los Llanos Gil, Salvador Martin Algarra, Elisabeth Perez-Ruiz, Ivan Marquez-Rodas, Delvys Rodriguez-Abreu, Remedios Blanco, Teresa Puertolas, Maria Angeles Royo, Rafael Rosell
Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR...
2018: Therapeutic Advances in Medical Oncology
Malgorzata Milewska, Mattia Cremona, Clare Morgan, John O'Shea, Aoife Carr, Sri H Velanki, Ann M Hopkins, Sinead Toomey, Stephen F Madden, Bryan T Hennessy, Alex J Eustace
Background: The application of genomic technologies to patient tumor samples identified groups of signaling pathways which acquire activating mutations. Some cancers are dependent on these mutations and the aberrant proteins resulting from these mutations can be targeted by novel drugs which can eradicate the cancer. Methods: We used to determine the frequency of ERBB mutations in solid tumors. We then determined the sensitivity of a panel of cell lines to clinically available PI3K inhibitors...
2018: Therapeutic Advances in Medical Oncology
Alessia Cavo, Alessandra Rubagotti, Elisa Zanardi, Chiara Fabbroni, Linda Zinoli, Antonio Di Meglio, Eleonora Arboscello, Andrea Bellodi, Paolo Spallarossa, Carlo Cattrini, Carlo Messina, Francesco Boccardo
Background: The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. Methods: This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- versus post-docetaxel)...
2018: Therapeutic Advances in Medical Oncology
Irene Moya-Horno, Santiago Viteri, Niki Karachaliou, Rafael Rosell
Treatment for advanced non-small cell lung cancer (NSCLC) has been significantly improved in recent years with the incorporation of drugs targeting antiangiogenesis and more specifically genomic alterations such as the EGFR mutations and ALK translocations. However, most patients invariably progress and die. The emergence of immune checkpoint inhibitors targeting the pathways involved in tumor-induced immunosuppression have redefined the management of the disease, achieving significant long-lasting responses with manageable safety profiles, regardless of histology...
2018: Therapeutic Advances in Medical Oncology
Thomas Walle, Rafael Martinez Monge, Adelheid Cerwenka, Daniel Ajona, Ignacio Melero, Fernando Lecanda
Radiotherapy (RT) is currently used in more than 50% of cancer patients during the course of their disease in the curative, adjuvant or palliative setting. RT achieves good local control of tumor growth, conferring DNA damage and impacting tumor vasculature and the immune system. Formerly regarded as a merely immunosuppressive treatment, pre- and clinical observations indicate that the therapeutic effect of RT is partially immune mediated. In some instances, RT synergizes with immunotherapy (IT), through different mechanisms promoting an effective antitumor immune response...
2018: Therapeutic Advances in Medical Oncology
Berardi Rossana, Partelli Stefano, Cascinu Stefano, Falconi Massimo
No abstract text is available yet for this article.
December 2017: Therapeutic Advances in Medical Oncology
Zhi Yang, Shuai Jiang, Yicheng Cheng, Tian Li, Wei Hu, Zhiqiang Ma, Fulin Chen, Yang Yang
Forkhead box C1 (FOXC1) is an essential member of the forkhead box transcription factors and has been highlighted as an important transcriptional regulator of crucial proteins associated with a wide variety of carcinomas. FOXC1 regulates tumor-associated genes and is regulated by multiple pathways that control its mRNA expression and protein activity. Aberrant FOXC1 expression is involved in diverse tumorigenic processes, such as abnormal cell proliferation, cancer stem cell maintenance, cancer migration, and angiogenesis...
December 2017: Therapeutic Advances in Medical Oncology
Rodica Di Lorenzo, Manmeet S Ahluwalia
Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities...
December 2017: Therapeutic Advances in Medical Oncology
Fanny Jean, Pascale Tomasini, Fabrice Barlesi
Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC...
December 2017: Therapeutic Advances in Medical Oncology
Alessandro De Vita, Federica Recine, Laura Mercatali, Giacomo Miserocchi, Chiara Liverani, Chiara Spadazzi, Roberto Casadei, Alberto Bongiovanni, Federica Pieri, Nada Riva, Dino Amadori, Toni Ibrahim
Background: Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models...
December 2017: Therapeutic Advances in Medical Oncology
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