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A large international study identifies potential new treatments to eliminate deadly tumours.
Posted On: January 09, 2017
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Cancer of the brain and spinal cord is the deadliest form of childhood cancer: it accounts for 34% of all childhood cancer deaths.
Atypical teratoid rhabdoid tumours (ATRTs) are a rare form of cancer that occurs primarily in children under the age of four. The disease is characterized by aggressive and difficult-to-treat tumours that grow in the brain and spinal cord. Most patients succumb to the disease within a year of their diagnosis. To improve these dismal outcomes, new therapeutic approaches to treat ATRTs are desperately needed.
A large international study co-led by PM Scientist Dr. Daniel De Carvalho has provided unprecedented insight into the biology of ATRTs and new strategies to treat them. The study team consists of over 100 researchers from cancer centres worldwide.
For the study, the researchers examined the genome sequence and structure of over 200 tumours. Based on this information, all tumours could be assigned to one of three subgroups, each of which displayed a different sensitivity to conventional and experimental cancer drugs. Importantly, tumours of a particular subgroup, which represent the most aggressive and treatment-resistant forms of the disease, were shown to be sensitive to dasatinib and nilotinib, two widely-used cancer drugs. Dasatinib and nilotinib are prescribed for leukemia and other cancers, but have not yet been tested for their ability to treat ATRTs.
These findings identify new potential drugs and targets to treat the different subgroups of ATRT. Moreover, the genomic information collected for the study is publicly available and provides researchers worldwide with a rich resource that can be used to design new ATRT drugs. "Only by fully understanding the molecular mechanisms driving cancer growth will we be able to develop effective strategies to cure this deadly disease," says Dr. De Carvalho of the study.
Follow this link to watch a video of Dr. De Carvalho describing the work.
This work was supported by Genome Canada, the Canadian Cancer Society, b.r.a.i.n.child, the C17 Childhood Cancer and Blood Disorders Research Network, Childhood Cancer Canada, Coast to Coast Against Cancer Foundation, the Kids with Cancer Society, the Government of Ontario, Brain Canada, the Canadian Institutes of Health Research, The Princess Margaret Cancer Foundation and generous donations from Mitchell Duckman, Tal Doron and Suri Boon.
Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M, Yu M, Gendoo DM, Dzamba M, Barszczyk M, Medina T, Riemenschneider AN, Morrissy AS, Ra YS, Ramaswamy V, Remke M, Dunham CP, Yip S, Ng HK, Lu JQ, Mehta V, Albrecht S, Pimentel J, Chan JA, Somers GR, Faria CC, Roque L, Fouladi M, Hoffman LM, Moore AS, Wang Y, Choi SA, Hansford JR, Catchpoole D, Birks DK, Foreman NK, Strother D, Klekner A, Bognár L, Garami M, Hauser P, Hortobágyi T, Wilson B, Hukin J, Carret AS, Van Meter TE, Hwang EI, Gajjar A, Chiou SH, Nakamura H, Toledano H, Fried I, Fults D, Wataya T, Fryer C, Eisenstat DD, Scheinemann K, Fleming AJ, Johnston DL, Michaud J, Zelcer S, Hammond R, Afzal S, Ramsay DA, Sirachainan N, Hongeng S, Larbcharoensub N, Grundy RG, Lulla RR, Fangusaro JR, Druker H, Bartels U, Grant R, Malkin D, McGlade CJ, Nicolaides T, Tihan T, Phillips J, Majewski J, Montpetit A, Bourque G, Bader GD, Reddy AT, Gillespie GY, Warmuth-Metz M, Rutkowski S, Tabori U, Lupien M, Brudno M, Schüller U, Pietsch T, Judkins AR, Hawkins CE, Bouffet E, Kim SK, Dirks PB, Taylor MD, Erdreich-Epstein A, Arrowsmith CH, De Carvalho DD, Rutka JT, Jabado N, Huang A. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. Cancer Cell. 2016 Dec 12. doi: 10.1016/j.ccell.2016.11.003
A large international study co-led by PM Scientist Dr. Daniel De Carvalho has provided unprecedented insight into the biology of ATRTs and new strategies to treat them. The study team consists of over 100 researchers from cancer centres worldwide.
For the study, the researchers examined the genome sequence and structure of over 200 tumours. Based on this information, all tumours could be assigned to one of three subgroups, each of which displayed a different sensitivity to conventional and experimental cancer drugs. Importantly, tumours of a particular subgroup, which represent the most aggressive and treatment-resistant forms of the disease, were shown to be sensitive to dasatinib and nilotinib, two widely-used cancer drugs. Dasatinib and nilotinib are prescribed for leukemia and other cancers, but have not yet been tested for their ability to treat ATRTs.
These findings identify new potential drugs and targets to treat the different subgroups of ATRT. Moreover, the genomic information collected for the study is publicly available and provides researchers worldwide with a rich resource that can be used to design new ATRT drugs. "Only by fully understanding the molecular mechanisms driving cancer growth will we be able to develop effective strategies to cure this deadly disease," says Dr. De Carvalho of the study.
Follow this link to watch a video of Dr. De Carvalho describing the work.
This work was supported by Genome Canada, the Canadian Cancer Society, b.r.a.i.n.child, the C17 Childhood Cancer and Blood Disorders Research Network, Childhood Cancer Canada, Coast to Coast Against Cancer Foundation, the Kids with Cancer Society, the Government of Ontario, Brain Canada, the Canadian Institutes of Health Research, The Princess Margaret Cancer Foundation and generous donations from Mitchell Duckman, Tal Doron and Suri Boon.
Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M, Yu M, Gendoo DM, Dzamba M, Barszczyk M, Medina T, Riemenschneider AN, Morrissy AS, Ra YS, Ramaswamy V, Remke M, Dunham CP, Yip S, Ng HK, Lu JQ, Mehta V, Albrecht S, Pimentel J, Chan JA, Somers GR, Faria CC, Roque L, Fouladi M, Hoffman LM, Moore AS, Wang Y, Choi SA, Hansford JR, Catchpoole D, Birks DK, Foreman NK, Strother D, Klekner A, Bognár L, Garami M, Hauser P, Hortobágyi T, Wilson B, Hukin J, Carret AS, Van Meter TE, Hwang EI, Gajjar A, Chiou SH, Nakamura H, Toledano H, Fried I, Fults D, Wataya T, Fryer C, Eisenstat DD, Scheinemann K, Fleming AJ, Johnston DL, Michaud J, Zelcer S, Hammond R, Afzal S, Ramsay DA, Sirachainan N, Hongeng S, Larbcharoensub N, Grundy RG, Lulla RR, Fangusaro JR, Druker H, Bartels U, Grant R, Malkin D, McGlade CJ, Nicolaides T, Tihan T, Phillips J, Majewski J, Montpetit A, Bourque G, Bader GD, Reddy AT, Gillespie GY, Warmuth-Metz M, Rutkowski S, Tabori U, Lupien M, Brudno M, Schüller U, Pietsch T, Judkins AR, Hawkins CE, Bouffet E, Kim SK, Dirks PB, Taylor MD, Erdreich-Epstein A, Arrowsmith CH, De Carvalho DD, Rutka JT, Jabado N, Huang A. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. Cancer Cell. 2016 Dec 12. doi: 10.1016/j.ccell.2016.11.003