Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma

Johnson, Brett; Mazor, Tali; Hong, Chibo; Barnes, Michael J.; Aihara, Koki; McLean, Cory Y.; Fouse, Shaun D.; Yamamoto, Shozo; Ueda, Hiroki; Tatsuno, Kenji; Asthana, Saurabh; Jalbert, Llewellyn E.; Nelson, Sarah J.; Bollen, Andrew W.; Gustafson, W. Clay; Charron, Elise; Weiss, William A.; Смирнов, Иван; Song, Jun S.; Olshen, Adam B.; Cha, Soonmee; Zhao, Yongjun; Moore, Richard A.; Mungall, Andrew J.; Jones, Steven J.M.; Hirst, Martin; Marra, Marco A.; Saito, Nobuhito; Aburatani, Hiroyuki; Mukasa, Akitake; Berger, Mitchel S.; Chang, Susan M.; Taylor, Barry S.; Costello, J

doi:10.1126/science.1239947

Cited by 1,154 publications

(1,094 citation statements)

References 56 publications

(46 reference statements)

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“…Exome sequencing of recurrent tumors revealed alterations in both the mTOR (MTOR, AKT, PTEN a.o.) and RB (RB, CDK4,6, CDKN2A) pathway (Johnson et al 2014). Similar events might be ongoing in NET, with potential impact on sequencing of therapies and support re-biopsy as a valuable tool for directing treatment.…”

Section: Impact Of Genomic Profiling On Therapymentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Pavel¹,

Sers²

2016

Endocrine-Related Cancer

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Neuroendocrine tumors (NETs) are a group of heterogenous neoplasms. Evidencebased treatment options for antiproliferative therapy include somatostatin analogues, the mTOR inhibitor everolimus, the multiple tyrosine kinase inhibitor sunitinib and peptide receptor radionuclide therapy with 177-Lu-octreotate. In the absence of definite predictive markers, therapeutic decision making follows clinical and pathological criteria. As objective response rates with targeted drugs are rather low, and response duration is limited in most patients, numerous combination therapies targeting multiple pathways have been explored in the field. Upfront combination of drugs, however, is associated with increasing toxicity and has shown little benefit. Major advancements in the molecular understanding of NET based on genomic, epigenomic and transcriptomic analysis have been achieved with prognostic and therapeutic impact. New insight into molecular alterations has paved the way to biomarker-driven clinical trials and may facilitate treatment stratification toward personalized medicine in the near future. However, an improved understanding of the complexity of pathway interactions is required for successful treatment. A systems biology approach is one of the tools that may help to achieve this endeavor.

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Section: Impact Of Genomic Profiling On Therapymentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Pavel¹,

Sers²

2016

Endocrine-Related Cancer

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“…A recent study identified a distinct mutation profile of recurrent glioma that varied from the initial mutation analyses in the same patient (24). The exomes of 23 initially low-grade gliomas and recurrent tumors resected from the same patients were sequenced and the mutation profiles were mutually compared.…”

Section: Perspectives On Novel Therapies For Gbmmentioning

confidence: 99%

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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Abstract. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single antiangiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.Glioblastoma multiforme (GBM) belongs to the largest group of primary central nervous system (CNS) tumors, so-called gliomas, which are formed from supporting glial cells in the brain parenchyma (1, 2). GBM represents the most common and most malignant tumor in this class, with an incidence of 3-4/100,000/year (3, 4). GBM is an extremely invasive and difficult to treat tumor, characterized by intense and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy (CHT). The current standard of care for patients with newly-diagnosed GBM comprises of neurosurgery and subsequent concomitant chemoradiotherapy by fractionated external-beam RT and systemic temozolomide followed by systemic temozolomide in the adjuvant setting (5). There are only very limited possibilities for the treatment of subsequent recurrences, generally with minimal clinical efficacy (6). Despite intensive multimodal treatment strategies, the median survival of patients with GBM is still 12.1-14.6 months and only 3-5% of patients survive longer than 3 years (7).Enormous progress has been made in the genetics and epigenetics of GBM during the past decade. The Cancer 21Τhis article is freely accessible online.Correspondence to: Jiri Polivka, Department of Neurology, Faculty Hospital Plzen, alej Svobody 80, 304 60, Plzen, Czech Republic. E-mail: polivka@fnplzen.cz Key Words: Glioblastoma multiforme, GBM, targeted therapy, immunotherapy, immune checkpoint inhibitors, PD1 inhibition, CTLA4 inhibition, clinical trials, personalized medicine, review. ANTICANCER RESEARCH 37: 21-34 (2017) [8][9][10][11][12]. The most important genetic...

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“…Glioma is a major therapeutic challenge due to numerous factors, including the tendency to adapt resistance against antiangiogenic agents, and intratumoural cellular heterogeneity that varies over the course of the disease and its treatment (3). To improve the poor prognosis for patients with glioma, it is important to understand the molecular mechanisms underlying and supporting tumor cell survival and invasion.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑509‑3p inhibits cell proliferation and invasion via downregulation of X‑linked inhibitor of apoptosis in glioma

Liao

et al. 2017

Oncol Lett

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Abstract. Malignant glioma is an aggressive type of cancer. Increasing evidence has suggested that microRNAs (miRs) regulate gene expression post-transcriptionally to affect cancer development and progression. Aberrant expression of miR-509-3p has been reported in cancer studies. However, the expression and mechanism of its function in glioma remains unclear. The present study demonstrated that miR-509-3p was downregulated in glioma tissue samples relative to non-tumor tissues, and that low miR-509-3p expression was associated with a reduced overall survival time. Functional studies revealed that the overexpression of miR-509-3p inhibited cell proliferation, induced apoptosis and suppressed cell migration and invasion via negatively regulating the expression of X-linked inhibitor of apoptosis. The data therefore suggested that miR-509-3p serves an important role in the development and progression of glioma, implicating its possible application in clinical practice as a biomarker and a potential novel therapeutic target.

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Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma

Cited by 1,154 publications

References 56 publications

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

MicroRNA‑509‑3p inhibits cell proliferation and invasion via downregulation of X‑linked inhibitor of apoptosis in glioma

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