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Article ; Online: UGDH promotes tumor-initiating cells and a fibroinflammatory tumor microenvironment in ovarian cancer.

Journal of experimental & clinical cancer research : CR

2023 Volume 42, Issue 1, Page(s) 270

Abstract: Background: Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of the gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC is driven by the survival of ...

Abstract	Background: Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of the gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC is driven by the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that are supported by a complex extracellular matrix and immunosuppressive microenvironment. To target TICs to prevent recurrence, we identified genes critical for TIC viability from a whole genome siRNA screen. A top hit was the cancer-associated, proteoglycan subunit synthesis enzyme UDP-glucose dehydrogenase (UGDH). Methods: Immunohistochemistry was used to characterize UGDH expression in histological and molecular subtypes of EOC. EOC cell lines were subtyped according to the molecular subtypes and the functional effects of modulating UGDH expression in vitro and in vivo in C1/Mesenchymal and C4/Differentiated subtype cell lines was examined. Results: High UGDH expression was observed in high-grade serous ovarian cancers and a distinctive survival prognostic for UGDH expression was revealed when serous cancers were stratified by molecular subtype. High UGDH was associated with a poor prognosis in the C1/Mesenchymal subtype and low UGDH was associated with poor prognosis in the C4/Differentiated subtype. Knockdown of UGDH in the C1/mesenchymal molecular subtype reduced spheroid formation and viability and reduced the CD133 + /ALDH Conclusions: These data show that modulation of UGDH expression in ovarian cancer reveals distinct roles for UGDH in the C1/Mesenchymal and C4/Differentiated molecular subtypes of EOC, influencing the tumor microenvironmental composition. UGDH is a strong potential therapeutic target in TICs, for the treatment of EOC, particularly in patients with the mesenchymal molecular subtype.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/pathology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Prognosis ; RNA, Small Interfering/genetics ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology ; Uridine Diphosphate Glucose Dehydrogenase/genetics ; Uridine Diphosphate Glucose Dehydrogenase/immunology
Chemical Substances	RNA, Small Interfering ; UGDH protein, human (EC 1.1.1.22) ; Uridine Diphosphate Glucose Dehydrogenase (EC 1.1.1.22)
Language	English
Publishing date	2023-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-023-02820-z
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Zs.A 2065: Show issues

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Article ; Online: Contrasting clinical characteristics and treatment patterns in women with newly diagnosed advanced-stage epithelial ovarian cancer in Australia, South Korea and Taiwan.

Chou, Hung-Hsueh / Fereday, Sian / DeFazio, Anna / Chang, Chih-Long / Bowtell, David / Hsu, Heng-Cheng / Traficante, Nadia / Jeong, Soo Young / Cheng, Wen-Fang / Ariyarantne, Dinuka / Tung, Teresa / Rajadhyaksha, Viraj / Lee, Won-Hee / Brown, David / Kim, Byoung-Gie

Journal of gynecologic oncology

2022 Volume 34, Issue 1, Page(s) e3

Abstract: Objective: The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation ...

Abstract	Objective: The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation of poly(ADP-ribose) polymerase inhibitors into clinical practice. Methods: Retrospective data from patients diagnosed with EOC (high-grade serous EOC for Taiwan) between January 2014 and December 2018 with ≥12 months follow-up from diagnosis were analyzed descriptively. Survival was evaluated by Kaplan-Meier with two-sided 95% confidence interval (CI). Results: Of the 987 patients (Australia, 223; S.Korea, 513; Taiwan, 251), 98% received platinum-based chemotherapy (CT). In S.Korea and Taiwan 76.0% and 78.9% respectively underwent primary cytoreductive surgery; in Australia, 56.5% had interval debulking surgery. Bevacizumab was included in primary/maintenance therapy for 22.4%, 14.6% and 6.8% of patients in Australia, S.Korea and Taiwan, respectively. Patients receiving bevacizumab were high-risk (reimbursement policy) and achieved similar real-world progression-free survival (PFS) compared with CT only. Overall, the median real-world PFS (months; 95% CI) was similar across Australia (16.0 [14.63-18.08]), S.Korea (17.7 [16.18-19.27]) and Taiwan (19.1 [17.56-22.29]). Conclusion: This study reveals poor prognosis despite differences in demographics and treatment patterns for patients with EOC across Asia-Pacific suggesting the need for biomarker-driven novel therapies to improve outcomes.
MeSH term(s)	Humans ; Female ; Carcinoma, Ovarian Epithelial/drug therapy ; Ovarian Neoplasms/therapy ; Ovarian Neoplasms/drug therapy ; Bevacizumab/therapeutic use ; Taiwan/epidemiology ; Retrospective Studies ; Neoadjuvant Therapy ; Republic of Korea/epidemiology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Cytoreduction Surgical Procedures
Chemical Substances	Bevacizumab (2S9ZZM9Q9V) ; Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2022-10-05
Publishing country	Korea (South)
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2478405-9
ISSN	2005-0399 ; 2005-0380
ISSN (online)	2005-0399
ISSN	2005-0380
DOI	10.3802/jgo.2023.34.e3
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Article ; Online: Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma.

Wang, Chen / Block, Matthew S / Cunningham, Julie M / Sherman, Mark E / McCauley, Bryan M / Armasu, Sebastian M / Vierkant, Robert A / Traficante, Nadia / Talhouk, Aline / Ramus, Susan J / Pejovic, Nadja / Köbel, Martin / Jorgensen, Brooke D / Garsed, Dale W / Fereday, Sian / Doherty, Jennifer A / Ariyaratne, Dinuka / Anglesio, Michael S / Widschwendter, Martin /

Pejovic, Tanja / Bosquet, Jesus Gonzalez / Bowtell, David D / Winham, Stacey J / Goode, Ellen L

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2023 Volume 32, Issue 4, Page(s) 542–549

Abstract: Background: Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior ... ...

Abstract	Background: Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior studies were largely platform-specific and unable to evaluate multiple molecular features. Methods: We analyzed genome-wide DNA methylation in 1,040 frozen HGSC, including 325 previously reported upon, seeking a multi-platform quantitative methylation signature that we evaluated in relation to clinical features, tumor characteristics, time to recurrence/death, extent of CD8+ tumor-infiltrating lymphocytes (TIL), gene expression molecular subtypes, and gene expression of the ATP-binding cassette transporter TAP1. Results: Methylation signature was associated with shorter time to recurrence, independent of clinical factors (N = 715 new set, hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.10-2.46; P = 0.015; N = 325 published set HR, 2.87; 95% CI, 2.17-3.81; P = 2.2 × 10-13) and remained prognostic after adjustment for gene expression molecular subtype and TAP1 expression (N = 599; HR, 2.22; 95% CI, 1.66-2.95; P = 4.1 × 10-8). Methylation signature was inversely related to CD8+ TIL levels (P = 2.4 × 10-7) and TAP1 expression (P = 0.0011) and was associated with gene expression molecular subtype (P = 5.9 × 10-4) in covariate-adjusted analysis. Conclusions: Multi-center analysis identified a novel quantitative tumor methylation signature of HGSC applicable to numerous commercially available platforms indicative of shorter time to recurrence/death, adjusting for other factors. Along with immune cell composition analysis, these results suggest a role for DNA methylation in the immunosuppressive microenvironment. Impact: This work aids in identification of targetable epigenome processes and stratification of patients for whom tailored treatment may be most beneficial.
MeSH term(s)	Female ; Humans ; Ovarian Neoplasms/pathology ; Prognosis ; Cystadenocarcinoma, Serous/genetics ; Cystadenocarcinoma, Serous/pathology ; Proportional Hazards Models ; DNA Methylation ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Tumor Microenvironment/genetics
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-22-0941
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Article ; Online: BRAF

JCO precision oncology

2022 Volume 2, Page(s) 1–14

Abstract: Purpose: Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic : Patients and methods: ... ...

Abstract	Purpose: Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic Patients and methods: Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic Results: Among patients with LGSC, nine (13.8%) of 65 had a somatic Conclusion: BRAF
Language	English
Publishing date	2022-01-27
Publishing country	United States
Document type	Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.17.00221
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Article: BRCA1

Nesic, Ksenija / Krais, John J / Vandenberg, Cassandra J / Wang, Yifan / Patel, Pooja / Cai, Kathy Q / Kwan, Tanya / Lieschke, Elizabeth / Ho, Gwo-Yaw / Barker, Holly E / Bedo, Justin / Casadei, Silvia / Farrell, Andrew / Radke, Marc / Shield-Artin, Kristy / Penington, Jocelyn S / Geissler, Franziska / Kyran, Elizabeth / Zhang, Fan /

Dobrovic, Alexander / Olesen, Inger / Kristeleit, Rebecca / Oza, Amit / Ratnayake, Gayanie / Traficante, Nadia / DeFazio, Anna / Bowtell, David D L / Harding, Thomas C / Lin, Kevin / Swisher, Elizabeth M / Kondrashova, Olga / Scott, Clare L / Johnson, Neil / Wakefield, Matthew J

medRxiv : the preprint server for health sciences

2023

Abstract: ... ...

Abstract	BRCA1
Language	English
Publishing date	2023-08-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.20.23287465
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Article: The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models.

Ho, Gwo Yaw / Vandenberg, Cassandra J / Lim, Ratana / Christie, Elizabeth L / Garsed, Dale W / Lieschke, Elizabeth / Nesic, Ksenija / Kondrashova, Olga / Ratnayake, Gayanie / Radke, Marc / Penington, Jocelyn S / Carmagnac, Amandine / Heong, Valerie / Kyran, Elizabeth L / Zhang, Fan / Traficante, Nadia / Huang, Ruby / Dobrovic, Alexander / Swisher, Elizabeth M /

McNally, Orla / Kee, Damien / Wakefield, Matthew J / Papenfuss, Anthony T / Bowtell, David D L / Barker, Holly E / Scott, Clare L

Therapeutic advances in medical oncology

2023 Volume 15, Page(s) 17588359231208674

Abstract: Background: Despite initial response to platinum-based chemotherapy and PARP inhibitor therapy (PARPi), nearly all recurrent high-grade serous ovarian cancer (HGSC) will acquire lethal drug resistance; indeed, ~15% of individuals have : Objectives: ... ...

Abstract	Background: Despite initial response to platinum-based chemotherapy and PARP inhibitor therapy (PARPi), nearly all recurrent high-grade serous ovarian cancer (HGSC) will acquire lethal drug resistance; indeed, ~15% of individuals have Objectives: To determine the potential of anti-microtubule agent (AMA) therapy (paclitaxel, vinorelbine and eribulin) in platinum-resistant or refractory (PRR) HGSC by assessing response in patient-derived xenograft (PDX) models of HGSC. Design and methods: Of 13 PRR HGSC PDX, six were primary PRR, derived from chemotherapy-naïve samples (one was Results: Seven out of thirteen PRR PDX (54%) were sensitive to treatment with the AMA, eribulin (time to progressive disease (PD) ⩾100 days from the start of treatment) and 11 out of 13 PDX (85%) derived significant benefit from eribulin [time to harvest (TTH) for each PDX with Conclusion: The efficacy observed for eribulin in PRR HGSC PDX was similar to that observed for paclitaxel, which transformed ovarian cancer clinical practice. Eribulin is therefore worthy of further consideration in clinical trials, particularly in ovarian carcinoma with early failure of carboplatin/paclitaxel chemotherapy.
Language	English
Publishing date	2023-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359231208674
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Article ; Online: Evolution of core archetypal phenotypes in progressive high grade serous ovarian cancer.

Nature communications

2021 Volume 12, Issue 1, Page(s) 3039

Abstract: The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection of factors driving heterogeneity before and through adaptation to treatment, we profile single- ... ...

Abstract	The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection of factors driving heterogeneity before and through adaptation to treatment, we profile single-cell RNA-sequencing (scRNA-seq) transcriptomes of HGSOC tumors collected longitudinally during therapy. We analyze scRNA-seq data from two independent patient cohorts to reveal that HGSOC is driven by three archetypal phenotypes, defined as oncogenic states that describe the majority of the transcriptome variation. Using a multi-task learning approach to identify the biological tasks of each archetype, we identify metabolism and proliferation, cellular defense response, and DNA repair signaling as consistent cell states found across patients. Our analysis demonstrates a shift in favor of the metabolism and proliferation archetype versus cellular defense response archetype in cancer cells that received multiple lines of treatment. While archetypes are not consistently associated with specific whole-genome driver mutations, they are closely associated with subclonal populations at the single-cell level, indicating that subclones within a tumor often specialize in unique biological tasks. Our study reveals the core archetypes found in progressive HGSOC and shows consistent enrichment of subclones with the metabolism and proliferation archetype as resistance is acquired to multiple lines of therapy.
MeSH term(s)	Cell Line, Tumor ; Cystadenocarcinoma, Serous/genetics ; DNA Repair ; Drug Resistance, Neoplasm ; Female ; Genetic Heterogeneity ; Humans ; Mutation ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Phenotype ; Sequence Analysis, RNA ; Transcriptome
Language	English
Publishing date	2021-05-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-23171-3
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Article ; Online: Transducin-Like Enhancer of Split 3 (TLE3) Expression Is Associated with Taxane Sensitivity in Nonserous Ovarian Carcinoma in a Three-Cohort Study.

Ring, Brian Z / Murali, Rajmohan / Soslow, Robert A / Bowtell, David D L / Fereday, Sian / deFazio, Anna / Traficante, Nadia / Kennedy, Catherine J / Brand, Alison / Sharma, Raghwa / Harnett, Paul / Samimi, Goli

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2018 Volume 27, Issue 6, Page(s) 680–688

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Bridged-Ring Compounds ; Co-Repressor Proteins/metabolism ; Cohort Studies ; Female ; Humans ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; Survival Rate ; Taxoids
Chemical Substances	Bridged-Ring Compounds ; Co-Repressor Proteins ; TLE3 protein, human ; Taxoids ; taxane (1605-68-1)
Language	English
Publishing date	2018-03-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-17-1101
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Article ; Online: Response rates to second-line platinum-based therapy in ovarian cancer patients challenge the clinical definition of platinum resistance.

Lindemann, Kristina / Gao, Bo / Mapagu, Cristina / Fereday, Sian / Emmanuel, Catherine / Alsop, Kathryn / Traficante, Nadia / Harnett, Paul R / Bowtell, David D L / deFazio, Anna

Gynecologic oncology

2018 Volume 150, Issue 2, Page(s) 239–246

Abstract: Objective: The aim of this study was to compare response rates and survival in women with "platinum resistant" epithelial ovarian cancer (EOC) who received further platinum-based or non‑platinum chemotherapy for treatment at first relapse.: Methods: ... ...

Abstract	Objective: The aim of this study was to compare response rates and survival in women with "platinum resistant" epithelial ovarian cancer (EOC) who received further platinum-based or non‑platinum chemotherapy for treatment at first relapse. Methods: Patients with high-grade EOC (including fallopian tube and peritoneal cancer) of all histologies recruited to the Australian Ovarian Cancer Study (AOCS) and treated with platinum-based primary chemotherapy were included. Response to second-line chemotherapy, overall survival (OS) and survival after treatment for first progression (OS2) were determined in all histologies and separately in women with high-grade serous tumors. Results: Of the 341 patients classified as platinum-resistant by the 6-month threshold, 243 (71%) were treated with chemotherapy at relapse. CA-125 response rates to platinum-based chemotherapy were significantly higher compared to non‑platinum chemotherapy (51% vs 21%, P < 0.001). Among patients with a platinum-free interval (PFI) of 3-6 months, OS2 in patients treated with platinum was significantly longer compared to individuals receiving non‑platinum-based treatment (median 17.67 months, 95% CI: 14.79-20.75 vs. 10.62 months, 95% CI: 8.02-12.72, P = 0.022). The patterns were similar when restricted to patients with high-grade serous histology. In patients with PFI <3 months, there was no significant difference in response or survival according to type of second-line treatment. Conclusions: Our findings further question the use of a 6-month PFI as an arbitrary threshold for subsequent treatment decision-making. Some patients considered "platinum resistant" still derive clinical benefit from platinum-based chemotherapy. Biomarkers of platinum sensitivity are needed in clinical practice to identify potential responders who should be offered re-treatment with platinum.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carcinoma, Ovarian Epithelial ; Cohort Studies ; Drug Resistance, Neoplasm ; Female ; Humans ; Middle Aged ; Neoplasms, Glandular and Epithelial/drug therapy ; Neoplasms, Glandular and Epithelial/pathology ; Organoplatinum Compounds/administration & dosage ; Organoplatinum Compounds/therapeutic use ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/pathology ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Organoplatinum Compounds
Language	English
Publishing date	2018-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2018.05.020
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Article ; Online: Clinical Utility of Real-Time Targeted Molecular Profiling in the Clinical Management of Ovarian Cancer: The ALLOCATE Study.

Kondrashova, Olga / Ho, Gwo-Yaw / Au-Yeung, George / Leas, Leakhena / Boughtwood, Tiffany / Alsop, Kathryn / Zapparoli, Giada / Dobrovic, Alexander / Ko, Yi-An / Hsu, Arthur L / Love, Clare J / Lunke, Sebastian / Wakefield, Matthew J / McNally, Orla / Quinn, Michael / Ananda, Sumitra / Neesham, Deborah / Hamilton, Anne / Grossi, Marisa /

Freimund, Alison / Kanjanapan, Yada / Rischin, Danny / Traficante, Nadia / Bowtell, David / Scott, Clare L / Christie, Michael / Taylor, Graham R / Mileshkin, Linda / Waring, Paul M

JCO precision oncology

2022 Volume 3, Page(s) 1–18

Abstract: Purpose: The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies.!## ...

Abstract	Purpose: The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies. Patients and methods: A total of 113 patients with ovarian cancer of varying histologies were recruited from two tertiary hospitals, with 99 patient cases suitable for prospective analysis. Targeted molecular and methylation profiling of fresh biopsy and archived tumor samples were performed by screening for mutations or copy-number variations in 44 genes and for promoter methylation of Results: Somatic genomic or methylation events were identified in 85% of all patient cases, with potentially actionable events with defined targeted therapies (including four resistance events) detected in 60% of all patient cases. On the basis of these findings, six patients received molecularly guided therapy, three patients had unsuspected germline cancer-associated Conclusion: ALLOCATE molecular profiling identified known genomic and methylation alterations of the different ovarian cancer subtypes and was deemed feasible and useful in routine clinical practice. Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling.
Language	English
Publishing date	2022-01-31
Publishing country	United States
Document type	Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.19.00019
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