Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2831
Amber Gonda, Jay V. Shah, Jake N. Siebert, Nanxia Zhao, M. Kwon, P. Moghe, Nicola L Francis, V. Ganapathy
{"title":"Abstract 2831: Exosome gene signatures characterize metastatic dynamicity","authors":"Amber Gonda, Jay V. Shah, Jake N. Siebert, Nanxia Zhao, M. Kwon, P. Moghe, Nicola L Francis, V. Ganapathy","doi":"10.1158/1538-7445.AM2021-2831","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2831","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48345612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-LB009
G. Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, M. Dadiani, A. Mayo, Coral Halperin, M. Pevsner-Fischer, H. Lavon, Shimrit Mayer, R. Nevo, Yan Stein, Nora Balint-Lahat, I. Barshack, H. R. Ali, C. Caldas, E. Gal-Yam, U. Alon, I. Amit, Ruth Scherz-Shouval
Cancer associated fibroblasts (CAFs) are prevalent in carcinomas. CAFs are also heterogeneous and perform various tumor-promoting tasks. Understanding whether distinct CAF-subsets exert specific functions, and how the composition of CAFs changes as tumors evolve could improve the accuracy of cancer treatment. Here, we analyzed thousands of CAFs by single-cell RNA-sequencing and index-sorting at several timepoints along breast tumor progression in mice, revealing distinct CAF-subsets. We discovered that the transcriptional programs of these subsets change over time, shifting from an immune-regulatory program at earlier timepoints to wound-healing and antigen-presenting programs at later timepoints, indicating that the composition and functions of CAFs are dynamic. We also found the two main CAF subsets in human breast tumors, wherein their ratio was associated with disease outcome. This association was particularly correlated with BRCA mutations in triple-negative breast cancer. Our findings indicate that the diverse composition of CAFs in breast cancer changes over time as tumors progress, and that these changes are linked to disease outcome. Citation Format: Gil Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, Maya Dadiani, Avi Mayo, Coral Halperin, Meirav Pevsner-Fischer, Hagar Lavon, Shimrit Mayer, Reinat Nevo, Yaniv Stein, Nora Balint-Lahat, Iris Barshack, H. Raza Ali, Carlos Caldas, Einav Nili Gal-Yam, Uri Alon, Ido Amit, Ruth Scherz-Shouval. Dynamic changes in the compositions of cancer associated-fibroblasts correlate with clinical outcome in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB009.
癌症相关成纤维细胞(CAFs)在癌症中普遍存在。caf也是异质的，执行各种促进肿瘤的任务。了解不同的caf亚群是否发挥特定的功能，以及caf的组成如何随着肿瘤的发展而变化，可以提高癌症治疗的准确性。在这里，我们通过单细胞rna测序和指数分选在小鼠乳腺肿瘤进展的几个时间点分析了数千种CAFs，揭示了不同的CAFs亚群。我们发现这些亚群的转录程序随着时间的推移而改变，从早期的免疫调节程序转变为后期的伤口愈合和抗原呈递程序，这表明CAFs的组成和功能是动态的。我们还在人类乳腺肿瘤中发现了两个主要的CAF亚群，其中它们的比例与疾病结局相关。这种关联与三阴性乳腺癌的BRCA突变尤其相关。我们的研究结果表明，随着肿瘤的进展，乳腺癌中cas的不同组成会随着时间的推移而变化，这些变化与疾病结局有关。引用格式:Gil Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, Maya Dadiani, Avi Mayo, Coral Halperin, Meirav Pevsner-Fischer, Hagar Lavon, Shimrit Mayer, Reinat Nevo, Yaniv Stein, Nora Balint-Lahat, Iris Barshack, H. Raza Ali, Carlos Caldas, Einav Nili Gal-Yam, Uri Alon, Ido Amit, Ruth Scherz-Shouval。癌症相关成纤维细胞组成的动态变化与乳腺癌的临床结局相关[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):摘要nr LB009。
{"title":"Abstract LB009: Dynamic changes in the compositions of cancer associated-fibroblasts correlate with clinical outcome in breast cancer","authors":"G. Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, M. Dadiani, A. Mayo, Coral Halperin, M. Pevsner-Fischer, H. Lavon, Shimrit Mayer, R. Nevo, Yan Stein, Nora Balint-Lahat, I. Barshack, H. R. Ali, C. Caldas, E. Gal-Yam, U. Alon, I. Amit, Ruth Scherz-Shouval","doi":"10.1158/1538-7445.AM2021-LB009","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB009","url":null,"abstract":"Cancer associated fibroblasts (CAFs) are prevalent in carcinomas. CAFs are also heterogeneous and perform various tumor-promoting tasks. Understanding whether distinct CAF-subsets exert specific functions, and how the composition of CAFs changes as tumors evolve could improve the accuracy of cancer treatment. Here, we analyzed thousands of CAFs by single-cell RNA-sequencing and index-sorting at several timepoints along breast tumor progression in mice, revealing distinct CAF-subsets. We discovered that the transcriptional programs of these subsets change over time, shifting from an immune-regulatory program at earlier timepoints to wound-healing and antigen-presenting programs at later timepoints, indicating that the composition and functions of CAFs are dynamic. We also found the two main CAF subsets in human breast tumors, wherein their ratio was associated with disease outcome. This association was particularly correlated with BRCA mutations in triple-negative breast cancer. Our findings indicate that the diverse composition of CAFs in breast cancer changes over time as tumors progress, and that these changes are linked to disease outcome. Citation Format: Gil Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, Maya Dadiani, Avi Mayo, Coral Halperin, Meirav Pevsner-Fischer, Hagar Lavon, Shimrit Mayer, Reinat Nevo, Yaniv Stein, Nora Balint-Lahat, Iris Barshack, H. Raza Ali, Carlos Caldas, Einav Nili Gal-Yam, Uri Alon, Ido Amit, Ruth Scherz-Shouval. Dynamic changes in the compositions of cancer associated-fibroblasts correlate with clinical outcome in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB009.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45309453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3096
Yan Xu, Qipeng Fan, R. Emerson
High grade serous ovarian cancer (HGSOC) is one of the most deadly and heterogenic cancers. We have recently shown that ZIP4 (gene name SLC39A4), a zinc transporter, is a novel cancer stem cell (CSC) marker in HGSOC. 100-200 ZIP4+, but not ZIP4-, cells from both PE04 and PEA2 cells formed larger tumors than those from 100-200 ALDH+ cells in mice. Mechanistically, we found that ZIP4 was an upstream regulator of another CSC-marker, NOTCH3, in HGSOC cells. NOTCH3 was functionally involved in spheroid formation in vitro and tumorigenesis in vivo in HGSOC. Drug-resistance is one of the main characteristics of CSCs, While ZIP4 converts drug-resistance to cisplatin (CDDP) and doxorubicin (DOX) as we reported previously, we unexpectedly found that ZIP4 induced a sensitization of HGSOC cells to histone deacetylase inhibitors (HDACis). In particular, only those HDACis against the Class IIa HDACs showed ZIP4-dependent sensitization. ZIP4 selectively up-regulated HDAC IIa HDACs, including HDAC4 and 5, with little or no effects to HDACs in other classes. ZIP4 knockout (KO) and HDAC4 knockdown (KD) increased cell resistance to LMK-235, a selective HDAC4/5 inhibitor. LMK-235 and HDAC4 knockdown (KD) inhibited spheroid formation in vitro and tumor development in vivo. Collectively, we revealed a novel ZIP4-NOTCH3-HDAC4 axis, which is functionally involved and important in CSC-related activities in vitro and tumorigenesis in vivo, and provide an innovative targeting strategy to CSC. Citation Format: Yan Xu, Qipeng Fan, Robert Emerson. A novel ZIP4-NOTCH3-HDAC4 axis in ovarian cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3096.
{"title":"Abstract 3096: A novel ZIP4-NOTCH3-HDAC4 axis in ovarian cancer stem cells","authors":"Yan Xu, Qipeng Fan, R. Emerson","doi":"10.1158/1538-7445.AM2021-3096","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3096","url":null,"abstract":"High grade serous ovarian cancer (HGSOC) is one of the most deadly and heterogenic cancers. We have recently shown that ZIP4 (gene name SLC39A4), a zinc transporter, is a novel cancer stem cell (CSC) marker in HGSOC. 100-200 ZIP4+, but not ZIP4-, cells from both PE04 and PEA2 cells formed larger tumors than those from 100-200 ALDH+ cells in mice. Mechanistically, we found that ZIP4 was an upstream regulator of another CSC-marker, NOTCH3, in HGSOC cells. NOTCH3 was functionally involved in spheroid formation in vitro and tumorigenesis in vivo in HGSOC. Drug-resistance is one of the main characteristics of CSCs, While ZIP4 converts drug-resistance to cisplatin (CDDP) and doxorubicin (DOX) as we reported previously, we unexpectedly found that ZIP4 induced a sensitization of HGSOC cells to histone deacetylase inhibitors (HDACis). In particular, only those HDACis against the Class IIa HDACs showed ZIP4-dependent sensitization. ZIP4 selectively up-regulated HDAC IIa HDACs, including HDAC4 and 5, with little or no effects to HDACs in other classes. ZIP4 knockout (KO) and HDAC4 knockdown (KD) increased cell resistance to LMK-235, a selective HDAC4/5 inhibitor. LMK-235 and HDAC4 knockdown (KD) inhibited spheroid formation in vitro and tumor development in vivo. Collectively, we revealed a novel ZIP4-NOTCH3-HDAC4 axis, which is functionally involved and important in CSC-related activities in vitro and tumorigenesis in vivo, and provide an innovative targeting strategy to CSC. Citation Format: Yan Xu, Qipeng Fan, Robert Emerson. A novel ZIP4-NOTCH3-HDAC4 axis in ovarian cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3096.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45914469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3176
Tzer-Min Kuo, Chin-Chan Lee, J. Lai, C. Su, M. Lai
{"title":"Abstract 3176: Inhibitory activity of Globo-H and SSEA-4 on activated T-cells","authors":"Tzer-Min Kuo, Chin-Chan Lee, J. Lai, C. Su, M. Lai","doi":"10.1158/1538-7445.AM2021-3176","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3176","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46261848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-LB250
N. Banerjee, Dianne W. Moore, Abhisek Gangrade, D. Buchsbaum, L. Nabors, T. Broker, L. Chow
Background: In the past few years, 3D organoid cultures of patient-derived tumors or patient-derived xenografts have gained significant attention as faster and more economical ex vivo alternatives to animal models for the pre-clinical evaluation of therapeutics. We reported previously that raft cultures of ex vivo epithelial warts, normal human epithelia from various anatomic sites, as well as cancer cell lines (cervical and melanoma) grown at the liquid:air interface recapitulate parental tissue phenotypes. Here we describe adaptation of the above technique to develop Organoid Raft Culture (ORC) of tumors of various origin and validation as preclinical models for drug evaluation. Methods: A stromal equivalent (SE) consisting of buffered rat-tail collagen and J2 mouse fibroblasts was prepared in 24-well tissue culture plates. Freshly harvested tumors from patients or patient-derived xenografts of cervical cancers were minced to Citation Format: Nilam Sanjib Banerjee, Dianne W. Moore, Abhisek Gangrade, Donald J. Buchsbaum, Luise Burt Nabors, Thomas R. Broker, Louise T. Chow. Development of organoid raft cultures of cervical, breast and glioblastoma tumors as quick economical ex vivo human cancer models for pre-clinical drug evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB250.
{"title":"Abstract LB250: Development of organoid raft cultures of cervical, breast and glioblastoma tumors as quick economical ex vivo human cancer models for pre-clinical drug evaluation","authors":"N. Banerjee, Dianne W. Moore, Abhisek Gangrade, D. Buchsbaum, L. Nabors, T. Broker, L. Chow","doi":"10.1158/1538-7445.AM2021-LB250","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB250","url":null,"abstract":"Background: In the past few years, 3D organoid cultures of patient-derived tumors or patient-derived xenografts have gained significant attention as faster and more economical ex vivo alternatives to animal models for the pre-clinical evaluation of therapeutics. We reported previously that raft cultures of ex vivo epithelial warts, normal human epithelia from various anatomic sites, as well as cancer cell lines (cervical and melanoma) grown at the liquid:air interface recapitulate parental tissue phenotypes. Here we describe adaptation of the above technique to develop Organoid Raft Culture (ORC) of tumors of various origin and validation as preclinical models for drug evaluation. Methods: A stromal equivalent (SE) consisting of buffered rat-tail collagen and J2 mouse fibroblasts was prepared in 24-well tissue culture plates. Freshly harvested tumors from patients or patient-derived xenografts of cervical cancers were minced to Citation Format: Nilam Sanjib Banerjee, Dianne W. Moore, Abhisek Gangrade, Donald J. Buchsbaum, Luise Burt Nabors, Thomas R. Broker, Louise T. Chow. Development of organoid raft cultures of cervical, breast and glioblastoma tumors as quick economical ex vivo human cancer models for pre-clinical drug evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB250.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46491860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.am2021-3173
K. Raghavan, Debora Vendramini, R. Francescone, J. Franco-Barraza, E. Cukierman
{"title":"Abstract 3173: NetrinG1's pro-tumor role on stroma-derived extracellular vesicles in pancreatic cancer","authors":"K. Raghavan, Debora Vendramini, R. Francescone, J. Franco-Barraza, E. Cukierman","doi":"10.1158/1538-7445.am2021-3173","DOIUrl":"https://doi.org/10.1158/1538-7445.am2021-3173","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42471343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2753
Elizabeth A. Yu, Wei Wu, Philippe Gui, C. McCoach, C. Blakely, S. Christenson, T. Bivona
{"title":"Abstract 2753: Deciphering macrophage function in lung tumor microenvironment and disease progression","authors":"Elizabeth A. Yu, Wei Wu, Philippe Gui, C. McCoach, C. Blakely, S. Christenson, T. Bivona","doi":"10.1158/1538-7445.AM2021-2753","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2753","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42856942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2666
Liping Li, Jung Hyun Kim, Wenyan Lu, Donna M. Williams, L. Xian, Joseph Kim, O. Rogers, R. Rampal, R. Koche, L. Cope, K. Reddy, D. Matson, Joe Zhao, J. Spivak, A. Moliterno, L. Resar
{"title":"Abstract 2666: HMGA1: An epigenetic switch required for MPN progression by inducingGATA-2and cell cycle progression through enhancer rewiring","authors":"Liping Li, Jung Hyun Kim, Wenyan Lu, Donna M. Williams, L. Xian, Joseph Kim, O. Rogers, R. Rampal, R. Koche, L. Cope, K. Reddy, D. Matson, Joe Zhao, J. Spivak, A. Moliterno, L. Resar","doi":"10.1158/1538-7445.AM2021-2666","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2666","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48035259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3143
A. Cani, Emily M Dolce, Elizabeth P. Darga, K. Hu, Martha E. Brown, C. Liu, J. Pierce, K. Bradbury, K. Aung, G. Schiavon, Danielle Carroll, T. Carr, T. Klinowska, J. Lindemann, G. Marshall, V. Rowlands, E. Harrington, J. Barrett, A. Armstrong, R. Baird, E. Hamilton, S. Im, K. Jhaveri, M. Patel, C. Dive, S. Tomlins, A. Udager, D. Hayes, C. Paoletti
Purpose: The vast majority of advanced ER POS breast cancers eventually cease responding to endocrine (ET) and other therapies leading to evolution of lethal disease. However, timely monitoring of the molecular events associated with response/progression in tissue biopsies is logistically difficult. The use of liquid biopsies, such as CTC and ctDNA, in this context has been of recent interest. Patients and Methods: Individual CTC and ctDNA were obtained at different time points from patients with advanced ER POS/HER2 NEG breast cancer enrolled in a Phase I trial of AZD9496, an oral selective estrogen receptor degrader (SERD) ET. The CTC, purified using tandem CellSearch®/DepArray™ technologies, were genomically profiled by DNA single cell next generation sequencing (scNGS). Plasma ctDNA was isolated from blood collected in Streck BCT tubes. Genomic profiling was performed by targeted gene panel scNGS for CTC and ddPCR for ERα gene (ESR1) mutations in ctDNA. Results: 123 high-quality CTCs from 12 patients profiled by scNGS showed 100% concordance with ctDNA in detection of driver ESR1 somatic mutations. CTC scNGS additionally revealed extensive intra-patient heterogeneity of driver alterations, that would have been unresolvable by bulk ctDNA profiling, including separate subclonal CTC populations emerging within the same patient. ScNGS revealed potential opportunities for targeted therapies in 73% of patients, directed at alterations in PIK3CA, FGFR2, KIT and BRAF, at times present as 2 or more targets in the same or different cell populations. In one patient, an emergent, distinct, BRAF p.V600E targetable alteration was detected in a subpopulation of CTCs collected at the progression time point but not at baseline. Conclusion: Serial monitoring of CTC and ctDNA genomic alterations is feasible and should enable real-time tracking of response/progression, tumor evolution and opportunities for precision medicine interventions. Citation Format: Andi K. Cani, Emily M. Dolce, Elizabeth P. Darga, Kevin Hu, Martha Brown, Chia-Jen Liu, Jackie Pierce, Kieran Bradbury, Kimberly Aung, Gaia Schiavon, Danielle Carroll, T. H. Carr, Teresa Klinowska, Justin Lindemann, Gayle Marshall, Vicky Rowlands, Elizabeth A. Harrington, J. Barrett, Anne Armstrong, Richard Baird, Erika Hamilton, Seock-Ah Im, Komal Jhaveri, Manish R. Patel, Caroline Dive, Scott A. Tomlins, Aaron M. Udager, Daniel F. Hayes, Costanza Paoletti. Monitoring circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) genomic alterations in ER positive (POS)/HER2 negative (NEG) advanced breast cancer during endocrine therapy: correlative study of AZD9496 oral SERD phase I trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3143.
{"title":"Abstract 3143: Monitoring circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) genomic alterations in ER positive (POS)/HER2 negative (NEG) advanced breast cancer during endocrine therapy: correlative study of AZD9496 oral SERD phase I trial","authors":"A. Cani, Emily M Dolce, Elizabeth P. Darga, K. Hu, Martha E. Brown, C. Liu, J. Pierce, K. Bradbury, K. Aung, G. Schiavon, Danielle Carroll, T. Carr, T. Klinowska, J. Lindemann, G. Marshall, V. Rowlands, E. Harrington, J. Barrett, A. Armstrong, R. Baird, E. Hamilton, S. Im, K. Jhaveri, M. Patel, C. Dive, S. Tomlins, A. Udager, D. Hayes, C. Paoletti","doi":"10.1158/1538-7445.AM2021-3143","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3143","url":null,"abstract":"Purpose: The vast majority of advanced ER POS breast cancers eventually cease responding to endocrine (ET) and other therapies leading to evolution of lethal disease. However, timely monitoring of the molecular events associated with response/progression in tissue biopsies is logistically difficult. The use of liquid biopsies, such as CTC and ctDNA, in this context has been of recent interest. Patients and Methods: Individual CTC and ctDNA were obtained at different time points from patients with advanced ER POS/HER2 NEG breast cancer enrolled in a Phase I trial of AZD9496, an oral selective estrogen receptor degrader (SERD) ET. The CTC, purified using tandem CellSearch®/DepArray™ technologies, were genomically profiled by DNA single cell next generation sequencing (scNGS). Plasma ctDNA was isolated from blood collected in Streck BCT tubes. Genomic profiling was performed by targeted gene panel scNGS for CTC and ddPCR for ERα gene (ESR1) mutations in ctDNA. Results: 123 high-quality CTCs from 12 patients profiled by scNGS showed 100% concordance with ctDNA in detection of driver ESR1 somatic mutations. CTC scNGS additionally revealed extensive intra-patient heterogeneity of driver alterations, that would have been unresolvable by bulk ctDNA profiling, including separate subclonal CTC populations emerging within the same patient. ScNGS revealed potential opportunities for targeted therapies in 73% of patients, directed at alterations in PIK3CA, FGFR2, KIT and BRAF, at times present as 2 or more targets in the same or different cell populations. In one patient, an emergent, distinct, BRAF p.V600E targetable alteration was detected in a subpopulation of CTCs collected at the progression time point but not at baseline. Conclusion: Serial monitoring of CTC and ctDNA genomic alterations is feasible and should enable real-time tracking of response/progression, tumor evolution and opportunities for precision medicine interventions. Citation Format: Andi K. Cani, Emily M. Dolce, Elizabeth P. Darga, Kevin Hu, Martha Brown, Chia-Jen Liu, Jackie Pierce, Kieran Bradbury, Kimberly Aung, Gaia Schiavon, Danielle Carroll, T. H. Carr, Teresa Klinowska, Justin Lindemann, Gayle Marshall, Vicky Rowlands, Elizabeth A. Harrington, J. Barrett, Anne Armstrong, Richard Baird, Erika Hamilton, Seock-Ah Im, Komal Jhaveri, Manish R. Patel, Caroline Dive, Scott A. Tomlins, Aaron M. Udager, Daniel F. Hayes, Costanza Paoletti. Monitoring circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) genomic alterations in ER positive (POS)/HER2 negative (NEG) advanced breast cancer during endocrine therapy: correlative study of AZD9496 oral SERD phase I trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3143.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48148360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：