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https://www.readbyqxmd.com/read/29760046/dual-hdac-and-pi3k-inhibition-abrogates-nf%C3%AE%C2%BAb-and-foxm1-mediated-dna-damage-response-to-radiosensitize-pediatric-high-grade-gliomas
#1
Sharmistha Pal, David Kozono, Xiaodong Yang, Wojciech Fendler, Whitney Fitts, Jing Ni, John A Alberta, Jean Zhao, Kevin X Liu, Jie Bian, Nathalene Truffaux, William A Weiss, Adam C Resnick, Pratiti Bandopadhayay, Keith L Ligon, Steven G Dubois, Sabine Mueller, Dipanjan Chowdhury, Daphne A Haas-Kogan
Aberrant chromatin remodeling and activation of the phosphatidylinositol 3-kinase (PI3K) pathway have been identified as important mediators of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) pathogenesis. As inhibition of these pathways are promising therapeutic avenues and radiation is the only modality to prolong survival of DIPG patients, we sought to explore radiosensitizing functions of such inhibition and explore mechanisms of action of such agents. Here we demonstrate that combined treatment with radiotherapy and CUDC-907, a novel first-in-class dual inhibitor of histone deacetylases (HDAC) and PI3K, evokes a potent cytotoxic response in pHGG and DIPG models...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29686020/workshop-report-for-cancer-research-defining-the-shades-of-gy-utilizing-the-biological-consequences-of-radiotherapy-in-the-development-of-new-treatment-approaches-meeting-viewpoint
#2
Mansoor M Ahmed, C Norman Coleman, Marc Mendonca, Soren Bentzen, Bhadrasain Vikram, Stephen M Seltzer, Dudley Goodhead, Ceferino Obcemea, Radhe Mohan, Kevin M Prise, Jacek Capala, Deborah Citrin, Gary Kao, Molykutty Aryankalayil, Iris Eke, Jeffrey C Buchsbaum, Pataje G S Prasanna, Fei-Fei Liu, Quynh-Thu Le, Beverly Teicher, David G Kirsch, DeeDee Smart, Joel Tepper, Silvia Formenti, Daphne Haas-Kogan, David Raben, James Mitchell
No abstract text is available yet for this article.
April 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29619963/national-cancer-institute-workshop-on-proton-therapy-for-children-considerations-regarding-brainstem-injury
#3
REVIEW
Daphne Haas-Kogan, Daniel Indelicato, Harald Paganetti, Natia Esiashvili, Anita Mahajan, Torunn Yock, Stella Flampouri, Shannon MacDonald, Maryam Fouladi, Kry Stephen, John Kalapurakal, Stephanie Terezakis, Hanne Kooy, David Grosshans, Mike Makrigiorgos, Kavita Mishra, Tina Young Poussaint, Kenneth Cohen, Thomas Fitzgerald, Vinai Gondi, Arthur Liu, Jeff Michalski, Dragan Mirkovic, Radhe Mohan, Stephanie Perkins, Kenneth Wong, Bhadrasain Vikram, Jeff Buchsbaum, Larry Kun
PURPOSE: Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29603591/phase-i-study-of-vorinostat-in-combination-with-isotretinoin-in-patients-with-refractory-recurrent-neuroblastoma-a-new-approaches-to-neuroblastoma-therapy-nant-trial
#4
Navin Pinto, Steven G DuBois, Araz Marachelian, Scott J Diede, Agne Taraseviciute, Julia L Glade Bender, Denice Tsao-Wei, Susan G Groshen, Joel M Reid, Daphne A Haas-Kogan, C Patrick Reynolds, Min H Kang, Meredith S Irwin, Margaret E Macy, Judith G Villablanca, Katherine K Matthay, Julie R Park
BACKGROUND: Vorinostat combined with retinoids produces additive antitumor effects in preclinical studies of neuroblastoma. Higher systemic exposures of vorinostat than achieved in pediatric phase I trials with continuous daily dosing are necessary for in vivo increased histone acetylation and cytotoxic activity. We conducted a phase I trial in children with relapsed/refractory neuroblastoma to determine the maximum tolerated dose (MTD) of vorinostat on an interrupted schedule, escalating beyond the previously identified pediatric MTD...
March 30, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29575995/large-vessel-arteriopathy-after-cranial-radiation-therapy-in-pediatric-brain-tumor-survivors
#5
Matthew Nordstrom, Erin Felton, Katherine Sear, Benita Tamrazi, Joseph Torkildson, Karen Gauvain, Daphne A Haas-Kogan, Josephine Chen, Benedict Del Buono, Anuradha Banerjee, David Samuel, David Saloner, Bing Tian, Erika Roddy, Christopher Hess, Heather Fullerton, Sabine Mueller
Among childhood cancer survivors, increased stroke risk after cranial radiation therapy may be caused by radiation-induced arteriopathy, but limited data exist to support this hypothesis. Herein, we assess the timing and presence of cerebral arteriopathy identified by magnetic resonance angiography (MRA) after cranial radiation therapy in childhood brain tumor survivors. In a cohort of 115 pediatric brain tumor survivors, we performed chart abstraction and prospective annual follow-up to assess the presence of large vessel cerebral arteriopathy by MRA...
April 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29398153/impact-of-pemetrexed-on-intracranial-disease-control-and-radiation-necrosis-in-patients-with-brain-metastases-from-non-small-cell-lung-cancer-receiving-stereotactic-radiation
#6
Daniel N Cagney, Allison M Martin, Paul J Catalano, Zachary J Reitman, Gabrielle A Mezochow, Eudocia Q Lee, Patrick Y Wen, Stephanie E Weiss, Paul D Brown, Manmeet S Ahluwalia, Nils D Arvold, Shyam K Tanguturi, Daphne A Haas-Kogan, Brian M Alexander, Amanda J Redig, Ayal A Aizer
BACKGROUND: Pemetrexed is a folate antimetabolite used in the management of advanced adenocarcinoma of the lung. We sought to assess the impact of pemetrexed on intracranial disease control and radiation-related toxicity among patients with adenocarcinoma of the lung who received stereotactic radiation for brain metastases. MATERIALS/METHODS: We identified 149 patients with adenocarcinoma of the lung and newly diagnosed brain metastases without a targetable mutation receiving stereotactic radiation...
March 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#7
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29126306/the-future-of-radiobiology
#8
David G Kirsch, Max Diehn, Aparna H Kesarwala, Amit Maity, Meredith A Morgan, Julie K Schwarz, Robert Bristow, Sandra Demaria, Iris Eke, Robert J Griffin, Daphne Haas-Kogan, Geoff S Higgins, Alec C Kimmelman, Randall J Kimple, Isabelle M Lombaert, Li Ma, Brian Marples, Frank Pajonk, Catherine C Park, Dörthe Schaue, Phuoc T Tran, Henning Willers, Brad G Wouters, Eric J Bernhard
Innovation and progress in radiation oncology depend on discovery and insights realized through research in radiation biology. Radiobiology research has led to fundamental scientific insights, from the discovery of stem/progenitor cells to the definition of signal transduction pathways activated by ionizing radiation that are now recognized as integral to the DNA damage response (DDR). Radiobiological discoveries are guiding clinical trials that test radiation therapy combined with inhibitors of the DDR kinases DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM), ataxia telangiectasia related (ATR), and immune or cell cycle checkpoint inhibitors...
April 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28958992/identification-of-mek162-as-a-radiosensitizer-for-the-treatment-of-glioblastoma
#9
EDITORIAL
Ravi S Narayan, Ana Gasol, Paul L G Slangen, Fleur M G Cornelissen, Tonny Lagerweij, Hou Y Y E Veldman, Rogier Dik, Jaap van den Berg, Ben J Slotman, Tom Würdinger, Daphne A Haas-Kogan, Lukas J A Stalpers, Brigitta G Baumert, Bart A Westerman, Jan Theys, Peter Sminia
Glioblastoma (GBM) is a highly aggressive and lethal brain cancer type. PI3K and MAPK inhibitors have been studied preclinically in GBM as monotherapy, but not in combination with radiotherapy, which is a key component of the current standard treatment of GBM. In our study, GBM cell lines and patient representative primary cultures were grown as multicellular spheroids. Spheroids were treated with a panel of small-molecule drugs including MK2206, RAD001, BEZ235, MLN0128, and MEK162, alone and in combination with irradiation...
February 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28871998/peripheral-blood-biomarkers-associated-with-toxicity-and-treatment-characteristics-after-131-i-metaiodobenzylguanidine-therapy-in-patients-with-neuroblastoma
#10
Kevin Campbell, Erin E Karski, Aleksandra Olow, David A Edmondson, Ayano C Kohlgruber, Matthew Coleman, Daphne A Haas-Kogan, Katherine K Matthay, Steven G DuBois
PURPOSE: Few tools exist to predict clinical outcomes after radiopharmaceutical therapy. Our goal was to identify associations between blood-based biomarkers of radiation effect and clinical outcomes after (131)I-metaiodobenzylguanidine ((131)I-MIBG) therapy in patients with neuroblastoma. METHODS AND MATERIALS: We conducted a prospective, single-center cohort study in children with advanced neuroblastoma treated with (131)I-MIBG as monotherapy or in combination with systemic putative radiation sensitizers...
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28860053/blood-brain-barrier-adapted-precision-medicine-therapy-for-pediatric-brain-tumors
#11
Bernard L Marini, Lydia L Benitez, Andrew H Zureick, Ralph Salloum, Angela C Gauthier, Julia Brown, Yi-Mi Wu, Dan R Robinson, Chandan Kumar, Robert Lonigro, Pankaj Vats, Xuhong Cao, Katayoon Kasaian, Bailey Anderson, Brendan Mullan, Benjamin Chandler, Joseph R Linzey, Sandra I Camelo-Piragua, Sriram Venneti, Paul E McKeever, Kathryn A McFadden, Andrew P Lieberman, Noah Brown, Lina Shao, Marcia A S Leonard, Larry Junck, Erin McKean, Cormac O Maher, Hugh J L Garton, Karin M Muraszko, Shawn Hervey-Jumper, Jean M Mulcahy-Levy, Adam Green, Lindsey M Hoffman, Katie Dorris, Nicholas A Vitanza, Joanne Wang, Jonathan Schwartz, Rishi Lulla, Natasha Pillay Smiley, Miriam Bornhorst, Daphne A Haas-Kogan, Patricia L Robertson, Arul M Chinnaiyan, Rajen Mody, Carl Koschmann
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28759109/probing-the-phosphatidylinositol-3-kinase-mammalian-target-of-rapamycin-pathway-in-gliomas-a-phase-2-study-of-everolimus-for-recurrent-adult-low-grade-gliomas
#12
Michael Wahl, Susan M Chang, Joanna J Phillips, Annette M Molinaro, Joseph F Costello, Tali Mazor, Sanda Alexandrescu, Janine M Lupo, Sarah J Nelson, Mitchel Berger, Michael Prados, Jennie W Taylor, Nicholas Butowski, Jennifer L Clarke, Daphne Haas-Kogan
BACKGROUND: Activation of the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is common in patients with low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied in this population. METHODS: Fifty-eight patients with pathologic evidence of recurrence after they had initially been diagnosed with World Health Organization (WHO) grade II gliomas were enrolled into a prospective phase 2 clinical trial and received daily everolimus (RAD001) for 1 year or until progression...
December 1, 2017: Cancer
https://www.readbyqxmd.com/read/28733870/rethinking-childhood-ependymoma-a-retrospective-multi-center-analysis-reveals-poor-long-term-overall-survival
#13
Amanda E Marinoff, Clement Ma, Dongjing Guo, Matija Snuderl, Karen D Wright, Peter E Manley, Hasan Al-Sayegh, Claire E Sinai, Nicole J Ullrich, Karen Marcus, Daphne Haas-Kogan, Liliana Goumnerova, Wendy B London, Mark W Kieran, Susan N Chi, Jason Fangusaro, Pratiti Bandopadhayay
Ependymoma is the third most common brain tumor in children, but there is a paucity of large studies with more than 10 years of follow-up examining the long-term survival and recurrence patterns of this disease. We conducted a retrospective chart review of 103 pediatric patients with WHO Grades II/III intracranial ependymoma, who were treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Chicago's Ann & Robert H. Lurie Children's Hospital between 1985 and 2008, and an additional 360 ependymoma patients identified from the Surveillance Epidemiology and End Results (SEER) database...
October 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#14
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
September 2017: Radiation Research
https://www.readbyqxmd.com/read/28594597/a-cautionary-tale-risks-of-radiation-therapy-de-escalation-in-pediatric-malignancies
#15
Daphne A Haas-Kogan, Christopher A Devine, Kevin X Liu, Stephanie A Terezakis
No abstract text is available yet for this article.
August 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28444227/incidence-and-prognosis-of-patients-with-brain-metastases-at-diagnosis-of-systemic-malignancy-a-population-based-study
#16
Daniel N Cagney, Allison M Martin, Paul J Catalano, Amanda J Redig, Nancy U Lin, Eudocia Q Lee, Patrick Y Wen, Ian F Dunn, Wenya Linda Bi, Stephanie E Weiss, Daphne A Haas-Kogan, Brian M Alexander, Ayal A Aizer
Background: Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program. Methods: We identified 1302166 patients with diagnoses of nonhematologic malignancies originating outside of the CNS between 2010 and 2013 and described the incidence proportion and survival of patients with brain metastases...
October 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28422554/reply-to-j-stenman-et-al
#17
Michael P La Quaglia, Daphne Haas-Kogan, Julie Park, Susan G Kreissman, Daniel von Allmen, Andrew Davidoff, Wendy B London, Geetika Khanna
No abstract text is available yet for this article.
June 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28357536/pediatric-high-grade-glioma-current-molecular-landscape-and-therapeutic-approaches
#18
REVIEW
Steve Braunstein, David Raleigh, Ranjit Bindra, Sabine Mueller, Daphne Haas-Kogan
High-grade pediatric central nervous system glial tumors are comprised primarily of anaplastic astrocytomas (AA, WHO grade III) and glioblastomas (GBM, WHO grade IV). High-grade gliomas are most commonly diagnosed in the primary setting in children, but as in adults, they can also arise as a result of transformation of a low-grade malignancy, though with limited frequency in the pediatric population. The molecular genetics of high-grade gliomas in the pediatric population are distinct from their adult counterparts...
September 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28301662/brain-metastases-in-newly-diagnosed-breast-cancer-a-population-based-study
#19
Allison M Martin, Daniel N Cagney, Paul J Catalano, Laura E Warren, Jennifer R Bellon, Rinaa S Punglia, Elizabeth B Claus, Eudocia Q Lee, Patrick Y Wen, Daphne A Haas-Kogan, Brian M Alexander, Nancy U Lin, Ayal A Aizer
Importance: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. Objective: To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Design, Setting, and Participants: Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute...
August 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28292440/a-kinase-inhibitor-targeted-to-mtorc1-drives-regression-in-glioblastoma
#20
QiWen Fan, Ozlem Aksoy, Robyn A Wong, Shirin Ilkhanizadeh, Chris J Novotny, William C Gustafson, Albert Yi-Que Truong, Geraldine Cayanan, Erin F Simonds, Daphne Haas-Kogan, Joanna J Phillips, Theodore Nicolaides, Masanori Okaniwa, Kevan M Shokat, William A Weiss
Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Here, we compared RapaLink-1, a TORKi linked to rapamycin, with earlier-generation mTOR inhibitors. Compared with rapamycin and Rapalink-1, TORKi showed poor durability...
March 13, 2017: Cancer Cell
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