{"id":"https://openalex.org/W2397411172","doi":"https://doi.org/10.1634/theoncologist.2-1-1","title":"The Challenge of Developing New Therapies for Childhood Cancers","display_name":"The Challenge of Developing New Therapies for Childhood Cancers","publication_year":1997,"publication_date":"1997-02-01","ids":{"openalex":"https://openalex.org/W2397411172","doi":"https://doi.org/10.1634/theoncologist.2-1-1","mag":"2397411172","pmid":"https://pubmed.ncbi.nlm.nih.gov/10388032"},"language":"en","primary_location":{"id":"doi:10.1634/theoncologist.2-1-1","doi":"https://doi.org/10.1634/theoncologist.2-1-1","is_oa":true,"landing_page_url":"https://doi.org/10.1634/theoncologist.2-1-1","pdf_url":"https://theoncologist.onlinelibrary.wiley.com/doi/pdfdirect/10.1634/theoncologist.2-1-1","source":{"id":"https://openalex.org/S15523509","display_name":"The Oncologist","issn_l":"1083-7159","issn":["1083-7159","1549-490X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310316295","host_organization_name":"AlphaMed Press","host_organization_lineage":["https://openalex.org/P4310316295"],"host_organization_lineage_names":["AlphaMed Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Oncologist","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://theoncologist.onlinelibrary.wiley.com/doi/pdfdirect/10.1634/theoncologist.2-1-1","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5024249524","display_name":"Frank M. Balis","orcid":"https://orcid.org/0000-0002-8117-6926","observed_orcids":["https://orcid.org/0000-0002-8117-6926"]},"institutions":[{"id":"https://openalex.org/I4210123359","display_name":"National Cancer Institute","ror":"https://ror.org/02t771148","country_code":"UA","type":"facility","lineage":["https://openalex.org/I4210123359"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["UA","US"],"is_corresponding":true,"raw_author_name":"Frank M. Balis","raw_affiliation_strings":["Head, Pharmacology & Experimental Therapeutics Section Pediatric Branch, National Cancer Institute"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Head, Pharmacology & Experimental Therapeutics Section Pediatric Branch, National Cancer Institute","institution_ids":["https://openalex.org/I4210123359","https://openalex.org/I4210140884"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5024249524"],"corresponding_institution_ids":["https://openalex.org/I4210123359","https://openalex.org/I4210140884"],"apc_list":{"value":3852,"currency":"USD","value_usd":3852},"apc_paid":null,"fwci":0.4582,"has_fulltext":true,"cited_by_count":19,"citation_normalized_percentile":{"value":0.71004855,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":97},"biblio":{"volume":"2","issue":"1","first_page":"1","last_page":"1"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10950","display_name":"Acute Lymphoblastic Leukemia research","score":0.6128000020980835,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10950","display_name":"Acute Lymphoblastic Leukemia research","score":0.6128000020980835,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12547","display_name":"Pharmaceutical studies and practices","score":0.07490000128746033,"subfield":{"id":"https://openalex.org/subfields/2735","display_name":"Pediatrics, Perinatology and Child Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10129","display_name":"Glioma Diagnosis and Treatment","score":0.044599998742341995,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pediatric-cancer","display_name":"childhood cancer","score":0.9259999990463257},{"id":"https://openalex.org/keywords/pediatric-oncology-drug-development","display_name":"pediatric oncology drug development","score":0.6679999828338623},{"id":"https://openalex.org/keywords/maximum-tolerated-dose","display_name":"maximum tolerated dose","score":0.6769999861717224},{"id":"https://openalex.org/keywords/drug-toxicity-in-children","display_name":"drug toxicity in children","score":0.4860000014305115},{"id":"https://openalex.org/keywords/refractory-cancer","display_name":"refractory cancer","score":0.5609999895095825},{"id":"https://openalex.org/keywords/salvage-therapy","display_name":"salvage therapy","score":0.6549999713897705},{"id":"https://openalex.org/keywords/myeloablative-therapy","display_name":"myeloablative therapy","score":0.7900000214576721},{"id":"https://openalex.org/keywords/bone-marrow-transplantation","display_name":"bone marrow transplantation","score":0.8989999890327454},{"id":"https://openalex.org/keywords/neuroblastoma","display_name":"neuroblastoma","score":0.6629999876022339},{"id":"https://openalex.org/keywords/brain-tumors","display_name":"brain tumors","score":0.625},{"id":"https://openalex.org/keywords/retinoblastoma","display_name":"retinoblastoma","score":0.7300000190734863},{"id":"https://openalex.org/keywords/wilms-tumor","display_name":"Wilms tumor","score":0.9760000109672546},{"id":"https://openalex.org/keywords/combination-chemotherapy","display_name":"combination chemotherapy","score":0.3880000114440918},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.47999998927116394},{"id":"https://openalex.org/keywords/anticancer-agents","display_name":"anticancer agents","score":0.43299999833106995},{"id":"https://openalex.org/keywords/clinical-trial-design","display_name":"clinical trial design","score":0.33799999952316284}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.9186466932296753},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.5897331833839417},{"id":"https://openalex.org/C2776577112","wikidata":"https://www.wikidata.org/wiki/Q500695","display_name":"Retinoblastoma","level":3,"score":0.5830742120742798},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.563152015209198},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.4738065302371979},{"id":"https://openalex.org/C2992894027","wikidata":"https://www.wikidata.org/wiki/Q5097977","display_name":"Childhood cancer","level":3,"score":0.4672192335128784},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.45037001371383667},{"id":"https://openalex.org/C2776715637","wikidata":"https://www.wikidata.org/wiki/Q938205","display_name":"Neuroblastoma","level":3,"score":0.4223657250404358},{"id":"https://openalex.org/C2776938808","wikidata":"https://www.wikidata.org/wiki/Q1737977","display_name":"Germ cell tumors","level":3,"score":0.41217660903930664},{"id":"https://openalex.org/C187212893","wikidata":"https://www.wikidata.org/wiki/Q123028","display_name":"Pediatrics","level":1,"score":0.34884703159332275},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.33765193819999695},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.0},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1634/theoncologist.2-1-1","doi":"https://doi.org/10.1634/theoncologist.2-1-1","is_oa":true,"landing_page_url":"https://doi.org/10.1634/theoncologist.2-1-1","pdf_url":"https://theoncologist.onlinelibrary.wiley.com/doi/pdfdirect/10.1634/theoncologist.2-1-1","source":{"id":"https://openalex.org/S15523509","display_name":"The Oncologist","issn_l":"1083-7159","issn":["1083-7159","1549-490X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310316295","host_organization_name":"AlphaMed Press","host_organization_lineage":["https://openalex.org/P4310316295"],"host_organization_lineage_names":["AlphaMed Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Oncologist","raw_type":"journal-article"},{"id":"pmid:10388032","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/10388032","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The oncologist","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1634/theoncologist.2-1-1","doi":"https://doi.org/10.1634/theoncologist.2-1-1","is_oa":true,"landing_page_url":"https://doi.org/10.1634/theoncologist.2-1-1","pdf_url":"https://theoncologist.onlinelibrary.wiley.com/doi/pdfdirect/10.1634/theoncologist.2-1-1","source":{"id":"https://openalex.org/S15523509","display_name":"The Oncologist","issn_l":"1083-7159","issn":["1083-7159","1549-490X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310316295","host_organization_name":"AlphaMed Press","host_organization_lineage":["https://openalex.org/P4310316295"],"host_organization_lineage_names":["AlphaMed Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Oncologist","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.98580002784729,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2397411172.pdf","grobid_xml":"https://content.openalex.org/works/W2397411172.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2045346558","https://openalex.org/W7099877771","https://openalex.org/W2075281896","https://openalex.org/W2013021412","https://openalex.org/W2007363664","https://openalex.org/W2943236134","https://openalex.org/W58246343","https://openalex.org/W2153248101","https://openalex.org/W4245257726","https://openalex.org/W2464521054"],"abstract_inverted_index":{"The":[0,10,148,231,335,565,720,790],"current":[1,917,949],"standard":[2,83,193,226,262,703,812,828,855,918,950],"treatments":[3,194],"for":[4,14,85,91,104,140,157,206,384,547,586,732,784,802,851],"childhood":[5,56,87,106,141,163,469,548,785],"cancers":[6,57,164,312,470,495,549,806,914,944],"are":[7,200,204,217,284,292,299,314,323,550,787,808,991],"highly":[8,853],"successful.":[9,922],"five-year":[11],"survival":[12,842],"rates":[13,47],"all":[15],"children":[16,94,309,330,338,370,406,433,441,507,524,595],"diagnosed":[17,333,683],"with":[18,310,331,508,811,870],"cancer":[19,416,756],"in":[20,54,220,369,432,447,463,493,500,506,523,527,538,615,628,671,681,755,866,912,915,932,956,994],"the":[21,27,45,62,117,155,166,170,178,236,248,258,266,308,374,381,387,392,394,401,413,421,448,451,460,514,528,536,539,556,572,587,592,601,643,693,713,733,737,751,816,827,839,885,941,957,965,972,995],"late":[22],"1980s":[23],"approaches":[24,139,187,763,797,825,865,911],"70%,":[25],"and":[26,42,64,76,103,111,165,184,212,228,265,290,319,326,339,371,373,450,519,525,543,562,571,577,600,619,696,727,781,835,844,898,964,974,980],"outlook":[28],"continues":[29],"to":[30,61,101,129,161,295,301,341,362,412,457,474,497,533,581,584,612,651,668,700,777,826,833,859,905,928,940,948,986],"improve.":[31,195],"For":[32,390,663,805,879],"some":[33,105],"types":[34,113],"of":[35,66,114,147,181,233,238,250,257,261,268,287,304,329,337,386,415,428,465,481,513,516,541,558,568,574,591,604,690,692,702,715,722,736,793,818,821,838,943,967,976],"localized":[36],"embryonal":[37],"tumors,":[38,116,935],"such":[39,108],"as":[40,109,134,136,191,197,276,624],"retinoblastoma":[41],"Wilms'":[43],"tumor,":[44],"cure":[46],"approach":[48,71,80,850],"or":[49,458],"exceed":[50],"90%.":[51],"Our":[52],"success":[53],"treating":[55],"can":[58,173,634,678,937],"be":[59,174,475,498,531,582,613,636,652,669,679,742,800,831,891,902,938,984],"attributed":[60],"development":[63,180,567,792,966],"use":[65,267],"an":[67],"integrated,":[68],"multimodality":[69,813,951],"treatment":[70,84,138,186,207,263,289,545,718,762,814,824,849,856,864,910,942,970],"which":[72,169,216,775,889,916],"includes":[73],"surgery,":[74],"radiaton,":[75],"combination":[77],"chemotherapy.":[78],"This":[79,705],"has":[81,454,709],"become":[82],"most":[86],"solid":[88],"tumors.":[89,606],"However,":[90,177],"every":[92],"two":[93],"who":[95,222,313,434],"survive,":[96],"one":[97,820],"child":[98],"still":[99],"succumbs":[100],"cancer,":[102,482],"cancers,":[107,786],"neuroblastoma":[110],"certain":[112],"brain":[115],"prognosis":[118,934],"remains":[119,126],"poor.":[120],"Therefore,":[121],"despite":[122],"our":[123,192,466,748],"successes,":[124],"there":[125],"a":[127,144,255,408,426,552,687,846,852],"need":[128,156,580,611],"develop":[130],"new":[131,137,159,182,185,664,694,759,796,823,847,863,909,968,989],"chemotherapeutic":[132],"agents":[133,355,487,665],"well":[135,947],"cancers.":[142,334,510],"In":[143,306,420],"previous":[145],"volume":[146],"Oncologist":[149],"(1996;1:169-172),":[150],"Dr.":[151],"Charles":[152],"Pratt":[153],"discussed":[154],"developing":[158],"drugs":[160,183,343,393,570],"treat":[162],"mechanisms":[167],"by":[168,247,272,346,685,894],"clinical":[171,179,359,566,791,803],"trials":[172,283,322,431,446,504,521,599,609,649,729,982],"efficiently":[175,992],"conducted.":[176],"becomes":[188],"more":[189,198,285,293,436,476,779,903],"difficult":[190,832,858],"Clearly,":[196],"patients":[199,203,221,234,279,657,684,869],"cured,":[201],"fewer":[202],"available":[205],"on":[208,316,366,443,555,744,884],"conventional":[209,501,559,672,977],"phase":[210,213,317,320,429,444,502,517,560,575,639,647,660,673,706,725,978],"I":[211,318,430,445,518,561,576,608,661,726,979],"II":[214,321,503,520,563,578,640,648,674,707,728,981],"trials,":[215,641,675],"typically":[218],"performed":[219,425,505,522,614,680],"have":[223,296,424,471,489,925,929],"relapsed":[224],"after":[225],"front-line":[227,542,717],"salvage":[229,277,544],"therapy.":[230,253,305,704],"condition":[232],"at":[235],"time":[237],"entry":[239],"onto":[240,597,659],"investigational":[241,281,569,961],"drug":[242,282,962],"studies":[243,963],"is":[244,625,857,920],"also":[245,635,799,874],"affected":[246],"nature":[249],"their":[251,605,876],"prior":[252,361,699,895],"As":[254,747],"result":[256],"increasing":[259],"intensity":[260,540],"regimens":[264,546],"myeloablative":[269],"therapy":[270,783,919],"followed":[271],"bone":[273],"marrow":[274],"transplantation":[275],"therapy,":[278],"entering":[280,596,646,960],"intolerant":[286],"further":[288],"they":[291,924,936],"likely":[294],"tumors":[297],"that":[298,356,405,488,666,740,807,945,988],"refractory":[300,311],"any":[302],"form":[303],"essence,":[307],"entered":[315,357,658],"becoming":[324],"less":[325,327,620,653,921],"representative":[328],"newly":[332,682],"tolerance":[336,411],"adults":[340,526],"anticancer":[342],"was":[344,397],"reviewed":[345],"Marsoni":[347],"et":[348],"al.":[349],"(Cancer":[350],"Treat":[351],"Rep":[352],"1985;69:1263-1269).":[353],"Seventeen":[354],"into":[358,638,712],"testing":[360,677],"1980":[363],"were":[364,435],"studied":[365],"similar":[367],"schedules":[368],"adults,":[372],"pediatric":[375,395,452,724,996],"maximum":[376],"tolerated":[377],"dose":[378,632],"(MTD)":[379],"exceeded":[380],"adult":[382,402,461,479,494],"MTD":[383,396,453,462],"16":[385],"17":[388],"agents.":[389],"half":[391],"30%":[398],"higher":[399],"than":[400,418,439,478,656],"MTD,":[403],"suggesting":[404],"had":[407],"significantly":[409],"greater":[410,589,602],"toxicity":[414],"chemotherapy":[417,897],"adults.":[419,629],"1990s":[422,529],"we":[423],"number":[427,689],"heavily":[437,593,617,621,654,867],"pretreated":[438,594,618,622,655,868],"those":[440,745,913],"treated":[442,743,810],"1970s,":[449],"been":[455,472,710,926],"equivalent":[456],"below":[459],"several":[464,484,716],"trials.":[467,564,662,746],"Similarly,":[468],"considered":[473],"chemosensitive":[477],"forms":[480],"but":[483],"recently":[485],"approved":[486],"significant":[490,553],"antitumor":[491,877,930],"activity":[492,931],"appear":[496,667],"inactive":[499,670],"recurrent":[509,871],"Careful":[511],"meta-analysis":[512],"results":[515,557],"will":[530,741,798],"needed":[532],"determine":[534],"if":[535],"changes":[537,955],"having":[551],"impact":[554,817],"design":[573,714,721,973],"may":[579,610,830,873,890,901],"adjusted":[583],"account":[585,731],"apparent":[588],"intolerance":[590],"these":[598,794,822,862,908,954],"refractoriness":[603],"Phase":[607],"both":[616],"children,":[623],"currently":[626],"done":[627],"Limited":[630],"intrapatient":[631],"escalations":[633],"incorporated":[637,711],"because":[642,837],"patient":[644,738,958],"population":[645,739,959],"tends":[650],"additional":[676],"administering":[686],"limited":[688],"doses":[691],"agent":[695],"assessing":[697],"response":[698],"initiation":[701],"window":[708],"protocols.":[719],"future":[723],"must":[730,983],"changing":[734],"characteristics":[735],"knowledge":[749],"about":[750],"underlying":[752],"molecular":[753],"defects":[754],"cells":[757],"expands,":[758],"biologically":[760],"based":[761],"(e.g.,":[764],"tumor":[765,881],"vaccines,":[766],"differentiating":[767],"agents,":[768],"immunotherapy,":[769],"growth":[770],"factor":[771],"inhibitors,":[772],"gene":[773],"therapy),":[774],"promise":[776],"provide":[778],"rational":[780],"selective":[782],"being":[788],"discovered.":[789],"exciting":[795],"challenging":[801],"investigators.":[804],"successfully":[809],"regimens,":[815],"adding":[819],"regimen":[829],"detect":[834],"quantify,":[836],"already":[840],"high":[841],"rates;":[843],"substituting":[845],"unproven":[848],"successful":[854],"justify.":[860],"Evaluating":[861],"disease":[872],"underestimate":[875],"activity.":[878],"example,":[880],"vaccines":[882],"depend":[883],"patient's":[886],"immue":[887],"response,":[888],"substantially":[892],"suppressed":[893],"dose-intensive":[896],"radiation.":[899],"It":[900],"feasible":[904],"initially":[906],"test":[907],"Once":[923],"demonstrated":[927],"poor":[933],"applied":[939],"respond":[946],"treatments.":[952],"With":[953],"non-cytotoxic":[969],"approaches,":[971],"end-points":[975],"adapted":[985],"ensure":[987],"therapies":[990],"developed":[993],"population.":[997]},"counts_by_year":[{"year":2023,"cited_by_count":2},{"year":2020,"cited_by_count":1},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":2}],"updated_date":"2026-09-06T09:10:53.072986","created_date":"2016-06-24T00:00:00"}