第18回抗悪性腫瘍薬開発フォーラム『次世代テクノロジーは抗がん剤開発に何をもたらすか』 2015/2/21 @がん研究会がん研究所腫瘍バンクの利用における課題谷田部恭(YATABE, Yasushi)愛知県がんセンター遺伝子病理診断部
腫瘍細胞の含有量をどのように評価するか? ■腫瘍細胞が存在しなければその組織を用いた結果は意味をなさない。 ■腫瘍細胞の占有率が高い場合と低い場合とではその解釈を違える必要がある。 MD Anderson Cancer  Center BATTLE Program
Stages I-III Resected BATTLE-Prevention (in preparation) Pls: E. Kim – S. Swisher Stage IV Untreated BATTLE-FL (n=300) (started 6/2011, n=39) Pls: E. Kim – J. Heymach Stage IV Refractory BATTLE 1 (n=324) (completed, 11/2009) Pls: E. Kim – R. Herbst BATTLE 2 (n=400) (started 6/2011, n=163) Pl: V. Papadimitrakopoulou (MD Anders/Yale)
BATTLE-1 BATTLE-2 Primary endpoint: 8-week disease control Kim et al (Cancer Discovery 2011) and V. Papadimitrakopoulou (unpublished)
Core Needle Biopsy (CNB) SCC Necrosis Fibrosis Adequacy Biopsies for Molecular Profiling (DNA, RNA and Proteins) in NSCLC Refractory Tumors: BATTLE-1 = 270/324, 83% (3 CNBs and no FNA) BATTLE-2 (3/2012) = 147/163, 90% (5 CNBs and FNA)
•  DNA Exome-Seq •  mRNA-Seq (Whole Transcriptome, WT) •  miRNA-Seq (miRNA) Percentage of WT Reads Mapped: 10 CNB vs. 10 Resected Tumors Resected Circos Plot of CNB Sequenced
総検体数n=5020 (手術検体75%、生検・細胞診25%)
膵癌2006年
肺癌乳癌技場2006年主としてEUS-FNA (n=1560)
肺癌
乳癌技場
1995年総検体数n=5020 (手術検体75%、生検・細胞診25%)肺癌
乳癌技場2006年
……… Nat Med. 1999 Apr;5(4):459-63 Enrichment of epithelial cells for molecular studies Anirban Maitra¹ .², Ignacio I. Wistuba¹ , Arvind K. Virmani¹ , M. Sakaguchi¹ , Inwon Park¹, Amy Stucky¹, Sara Milchgrub², David Gibbons², John D. Minna¹,³,⁴ & Adi F. Gazdar¹,² 'Hamon Center for Therapeutic Oncology Research, and Departments of ²Pathology, ³Internal Medicine and ¹Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75235, USA Correspondence should be addressed to A.F.G.; email: gazdar@simmons.swmed.edu
1995年総検体数n=5020 (手術検体75%、生検・細胞診25%)肺癌
乳癌降帰
RNAの解析は、コピー数の違い、転写状態の違いから、腫瘍細胞をより反映する！ A New Era of Reverse Translational Research
Gopa Iyer,* Aphrothiti J. Hanrahan, Matthew I. Milowsky, Hikmat Al-Ahmadie, Sasinya N. Scott, Manickam Janakiraman, Mono Pirun, Chris Sander, Nicholas D. Socci, Irina Ostrovnaya, Agnes Viale, Adriana Heguy, Luke Peng, Timothy A. Chan, Bernard Bochner, Dean F. Bajorin, Michael F. Berger, Barry S. Taylor,† David B. Solit† A
- Purpose
The purpose of this study is to learn what effects, good and/or bad. Everolimus has on advanced urothelial cancer. The goal of this clinical research study is to learn if the study drug Everolimus can shrink or slow the growth of urothelial cancer. The this drug will also be studied. The patients physical state, changes in the size of the tumor, and laboratory findings taken while on-stu us decide if Everolimus is safe and effective.
Study Type: Study Design: Interventional Endpoint Classification: Safety/Efficacy Study Intervention Model; Single Group Assignment Masking: Open Label Primary Purpose: Treatment Official Title:      Phase II Study of Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium tesource links provided by NLM: Genetics Home Reference related topics:   bladder cancer MedlinePlus related topics:   Bladder Cancer   Cancer Drug Information available for:   Sirolimus   Everolimus   Temsirolimus U.S. FDA Resources Science. 2012 Oct 12;338(6104):221
Gopa Iyer,* Aphrothiti J. Hanrahan, Matthew I. Milowsky, Hikmat Al-Ahmadie, Sasinya N. Scott, Manickam Janakiraman, Mono Pirun, Chris Sander, Nicholas D. Socci, Irina Ostrovnaya, Agnes Viale, Adriana Heguy, Luke Peng, Timothy A. Chan, Bernard Bochner, Dean F. Bajorin, Michael F. Berger, Barry S. Taylor,† David B. Solit† Science. 2012 Oct 12;338(6104):221
Gopa Iyer,* Aphrothiti J. Hanrahan, Matthew I. Milowsky, Hikmat Al-Ahmadie, Sasinya N. Scott, Manickam Janakiraman, Mono Pirun, Chris Sander, Nicholas D. Socci, Irina Ostrovnaya, Agnes Viale, Adriana Heguy, Luke Peng, Timothy A. Chan, Bernard Bochner, Dean F. Bajorin, Michael F. Berger, Barry S. Taylor,† David B. Solit†
Marcin Imielinski,¹,²,³ Heidi Greulich,²,³,⁴ Bethany Kaplan,²,³ Luiz Araujo,⁵ Joseph Amann,⁵ Leora Horn,6 Joan Schiller,7 Miguel A. Villalona-Calero,5 Matthew Meyerson,²,³,⁸ and David P. Carbone⁵
Marcin Imielinski,¹,²,³ Heidi Greulich,²,³,⁴ Bethany Kaplan,²,³ Luiz Araujo,⁵ Joseph Amann,⁵ Leora Horn,6 Joan Schiller,7 Miguel A. Villalona-Calero,5 Matthew Meyerson,²,3,8 and David P. Carbone5
口腫瘍として採取された組織は、腫瘍細胞と正常細胞が常に混在して存在するため、腫瘍細胞の含有率によって評価を考察する必要がある。口組織採取方法、対象とする核酸によってはより腫瘍細胞を反映することができる。ロ組織バンクには、少なくとも腫瘍細胞含有率についての情報が必要である。ロReverse translational researchのような臨床からのアップローチは、まれな遺伝子変異に対する効率のよい検出方法であり、臨床治験の組織保存が重要になる。