Gene expression profiling in clinical practice The impact of Oncotype DX and EndoPredict on decision making with increasing oncological work experience

2018 ◽  
Author(s):  
C Eichler ◽  
J Fromme ◽  
J Puppe ◽  
W Malter ◽  
S Paepke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Decision Making ◽  
Clinical Practice ◽  
Gene Expression Profiling ◽  
Work Experience ◽  
Expression Profiling ◽  
Oncotype Dx ◽  
The Impact

scholarly journals Gene-expression Profiling – A Decision Impact Analysis: Decision Dependency on Oncotype DX® as a Function of Oncological Work Experience in 117 Cases

2018 ◽  
Vol 39 (1) ◽  
pp. 297-303 ◽  
Author(s):  
CHRISTIAN EICHLER ◽  
JULIA FROMME ◽  
FABINSHY THANGARAJAH ◽  
JULIAN PUPPE ◽  
STEFAN PAEPKE ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Work Experience ◽  
Expression Profiling ◽  
Impact Analysis ◽  
Oncotype Dx

Access to personalized medicine: Factors influencing the use and value of gene expression profiling in treatment decision making.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 10-10
Author(s):  
Yvonne Bombard ◽  
Linda Rozmovits ◽  
Maureen E. Trudeau ◽  
Natasha B. Leighl ◽  
Ken Deal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Decision Making ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Clinical Utility ◽  
Perceived Value ◽  
Treatment Decision ◽  
Treatment Decision Making ◽  
Comparison Results

10 Background: Genomic information is increasingly used to personalize health care. One example is gene-expression profiling (GEP) tests that estimate recurrence risk to inform chemotherapy decisions in breast cancer treatment. Recently, GEP tests were publicly funded in Ontario. We assessed the clinical utility of GEP tests, exploring the factors facilitating their use and value in treatment decision-making. Methods: As part of a mixed-methods clinical utility study, we conducted interviews with oncologists (n=14), and focus groups and interviews with breast cancer patients (n=28) who underwent GEP, recruited through oncology clinics in Ontario. Data were analyzed using content analysis and constant comparison. Results: Various factors governing access to GEP have given rise to challenges for patients and oncologists. Oncologists are positioned as gatekeepers of GEP, providing access in medically appropriate cases. However, varying perceptions of appropriateness led to perceived inequities in access and negative impacts on the doctor-patient relationship. Media attention facilitated patient awareness of GEP but complicated gatekeeping. Additional administration burden and long waits for results led to increased patient anxiety and delayed treatment. Collectively, these factors inadvertently heightened GEP’s perceived value for patients relative to other prognostic indicators because of barriers to access. Conclusions: This study delineates the factors facilitating and restricting access to GEP, and highlights the roles of the media and organization of services in GEP’s perceived value and utilization. Results identify a need for administrative changes and practice guidelines to support streamlined and standardized utilization of the test.

The basal subtype to predict clinical benefit from neoadjuvant chemotherapy: Final results from a phase II clinical trial of DDMVAC plus bevacizumab.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 291-291 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Woonyoung Choi ◽  
Sima P. Porten ◽  
Yu Shen ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Neoadjuvant Chemotherapy ◽  
Bone Metastases ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Urothelial Cancer ◽  
Basal Subtype ◽  
Clinical Trial Results ◽  
The Impact

291 Background: Gene expression profiling (GEP) suggests 3 main subtypes of urothelial cancer: basal, which historically has the worst prognosis with high proliferation and HIF-1 expression; p53-like, with decreased proliferation and increased markers of extracellular matrix (ECM); and luminal which has increased proliferation compared to p53-like tumors. We hypothesized that GEP of transurethral resections (TUR) and cystectomy specimens from patients on a neoadjuvant trial would predict benefit from chemotherapy. Methods: Sixty patients enrolled on a neoadjuvant trial of DDMVAC+B. TUR and cystectomy specimens were available for gene expression profiling in 39 and 33 patients, respectively, with matched specimens in 23 patients. The validation set consisted of 49 patients treated with perioperative MVAC on a previously published clinical trial. Results: Chemotherapy was quite active with pT0N0 and ≤ pT1N0 down-staging rates of 38% and 53%, respectively. Basal tumors had improved survival compared to luminal and p53-like (5-year OS 91%, 73% and 36%, p=0.015). A validation cohort of patients treated with perioperative MVAC confirmed this survival benefit (5-year OS basal, luminal, and p53-like 77%, 57%, and 57%, respectively, p =0.027). The use of bevacizumab in basal tumors did not confirm evidence of significant benefit in these small numbers of patients (5-year OS bevacizumab: 91% vs MVAC: 77%, p=0.68) Bone metastases within 2 years associated exclusively with the p53-like subtype (p53-like: 100%, luminal: 0%, basal 0%, p≤0.001). The p53-like subtype was enriched at cystectomy (basal to p53-like in 3/5 (60%), luminal to p53-like in 5/7 (71%), suggesting chemo-resistance in p53-like tumors. Conclusions: In contrast to historical expectations, the basal subtype was predictive of clinical outcomes from neoadjuvant chemotherapy, reflecting the impact of chemotherapy on highly proliferative tumors. Bone metastases were associated with the p53-like subtype which is enriched for ECM. We can no longer think of urothelial cancer as one disease; subtyping should be considered for all tumors, and may have implications on selecting therapy. Clinical trial information: NCT00506155.

scholarly journals Predictive and prognostic transcriptomic biomarkers in soft tissue sarcomas

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Eve Merry ◽  
Khin Thway ◽  
Robin L. Jones ◽  
Paul H. Huang
Keyword(s):  
Gene Expression ◽  
Clinical Practice ◽  
Soft Tissue ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cancer Biology ◽  
Treatment Strategies ◽  
Soft Tissue Sarcomas ◽  
Selective Treatment ◽  
Genomic Grade Index

AbstractSoft tissue sarcomas (STS) are rare and heterogeneous tumours comprising over 80 different histological subtypes. Treatment options remain limited in advanced STS with high rates of recurrence following resection of localised disease. Prognostication in clinical practice relies predominantly on histological grading systems as well as sarcoma nomograms. Rapid developments in gene expression profiling technologies presented opportunities for applications in sarcoma. Molecular profiling of sarcomas has improved our understanding of the cancer biology of these rare cancers and identified potential novel therapeutic targets. In particular, transcriptomic signatures could play a role in risk classification in sarcoma to aid prognostication. Unlike other solid and haematological malignancies, transcriptomic signatures have not yet reached routine clinical use in sarcomas. Herein, we evaluate early developments in gene expression profiling in sarcomas that laid the foundations for transcriptomic signature development. We discuss the development and clinical evaluation of key transcriptomic biomarker signatures in sarcomas, including Complexity INdex in SARComas (CINSARC), Genomic Grade Index, and hypoxia-associated signatures. Prospective validation of these transcriptomic signatures is required, and prospective trials are in progress to evaluate reliability for clinical application. We anticipate that integration of these gene expression signatures alongside existing prognosticators and other Omics methodologies, including proteomics and DNA methylation analysis, could improve the identification of ‘high-risk’ patients who would benefit from more aggressive or selective treatment strategies. Moving forward, the incorporation of these transcriptomic prognostication signatures in clinical practice will undoubtedly advance precision medicine in the routine clinical management of sarcoma patients.

scholarly journals DDRE-33. MOLECULAR DIFFERENTIATION OF IMIPRIDONES ONC201 AND ONC206

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii68-ii68
Author(s):  
Varun Prabhu ◽  
Caroline Cuoco ◽  
Jinkyu Jung ◽  
Sara Morrow ◽  
Abed Rahman Kawakibi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Acquired Resistance ◽  
Cross Resistance ◽  
Glioblastoma Cells ◽  
Biodistribution Studies ◽  
Allosteric Sites ◽  
Receptor Pharmacology ◽  
The Impact

Abstract ONC201 is the first bitopic antagonist of dopamine receptor D2 (DRD2) and agonist of ClpP in oncology. In clinical trials, the small molecule has induced durable tumor regressions and clinical benefit in H3 K27M-mutant glioma patients while being well tolerated. ONC206 is a chemical derivative of ONC201 with nanomolar anti-cancer potency. In this study, we describe receptor pharmacology, gene expression profiling, acquired resistance and biodistribution studies that suggest ONC206 exhibits distinct therapeutic properties relative to ONC201. ONC206 exhibited a nanomolar Ki for DRD2 with complete specificity across human GPCRs and complete DRD2 antagonism. Schild analyses of ONC206 in cAMP and β-Arrestin recruitment assays revealed hallmarks of non-competitive DRD2 antagonism, unlike antipsychotics but similar to ONC201. Shotgun mutagenesis across DRD2 identified 7 residues critical for ONC206-mediated antagonism at orthosteric and allosteric sites. Six residues were critical for ONC201 and ONC206, however the impact varied between the two compounds and one allosteric residue was exclusive to ONC206. Structural mapping revealed that some ONC206-critical allosteric residue interactions are located at the interface of TM-IV and –V that mediates the DRD2 homodimer interface. Gene expression profiling revealed ONC206 and ONC201 induce distinct signatures in U87 glioblastoma cells, further supporting distinct functional effects. Similarly, T98G glioblastoma cells with acquired resistance to ONC201 or ONC206 reveal partial cross resistance. Finally, rat biodistribution studies revealed nanomolar CSF concentrations that exceed therapeutic thresholds, unlike ONC201. In summary, ONC206 exhibits increased non-competitive DRD2 antagonism, nanomolar potency, distinct biodistribution, differentiated gene expression and disruption of DRD2 dimers relative to ONC201. Thus, ONC206 may be uniquely poised to address tumors that are not addressed by ONC201 or have developed acquired resistance.

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