Patient willingness to undergo pharmacodynamic and pharmacokinetic tests in early phase oncology trials

Tibes, Raoul; Piper, Barbara F.; Smith, Jessica A.; James, Raysenia L.; Benjamin, Martin; Yim, Jay H.; Ramanathan, Ramesh K.; Hoff, Daniel D. Von; Bay, R. Curtis; Borad, Mitesh J.

doi:10.1002/cncr.25885

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…172 Questions remain as to whether eligibility for future clinical studies should be restricted to WHO subtypes of MDS/MPN, such as a study for CMML patients alone versus broad inclusion of MDS/MPN-U patients, or whether the focus should be based on clinical disease phenotype or proliferative versus non-proliferative features. As we move forward with clinical studies based on targeted molecular pathways, these should ideally determine patient selection based upon 'founder' tyrosine kinase signaling pathway mutations or those with transcription factor mutations.…”

Section: Novel Strategies and Future Clinical Trial Designs For The Tmentioning

confidence: 99%

An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o n MDS/MPN: cytogenetic, molecular genetics and signaling abnormalitiesChromosome analysis using conventional cytogenetics and high-resolution single nucleotide polymorphism array karyotyping (SNP-A) reveals chromosome abnormalities in 70% of MDS/MPN patients. 7 Most of these are aneuploidies (trisomy 8, monosomy 7) or deletions (del7q, del13q, del20q); a minority have reciprocal translocations involving diverse tyrosine kinase (TK) fusion genes. 8,9 Some of these fusions are listed separately within the current WHO classification: 'myeloid and lymphoid neoplasms with eosinophilia' (MLN-eo) and abnormalities of PDGFRA, PDGFRB and FGFR1. Fusions involving other kinases are also seen in patients with MDS/MPN or MPNs. 10 Fusions involving PDGFRA, PDGFRB and ABL1 are important to recognize as they confer sensitivity to TK inhibitors (TKIs), such as imatinib. 11 Other fusions involving FGFR1 or JAK2 are insensitive to imatinib but may respond to ponatinib or ruxolitinib, respectively. [12][13][14][15][16] Most mutant genes fall into four functional classes: signaling, epigenetic, splicing and transcription ( Figure 2). [17][18][19][20] Signaling mutations result in aberrant activation of proliferative and anti-apoptotic pathways normally induced by growth factors (GFs). In addition to the TK gene fusions mentioned above, mutations have been described in GF receptors (CSF3R), downstream cytokine receptor signaling intermediates (JAK2, NRAS, KRAS) and negative regulators of signaling pathways (PTPN11, CBL, NF1). [21][22][23][24][25][26][27] Mutations involving RAS are demonstrable in 90% of JMML cases and may emerge as a defining feature of this condition. 28 Signaling mutations occur in approximately 50% of CMML patients and correlate with a myeloproliferative phenotype and enhancement of in vitro sensitivity to GM-CSF. 29 Up to 80% of patients with RARS-T have activated JAK-STAT signaling as a consequence of the presence of JAK2 V617F or mutations in MPL [encoding for the thrombopoietin receptor (Tpo-R)]. 30 In mice, abrogation of Notch signaling leads to a MDS/MPN phenotype, but its relevance in humans is unknown. 31 MDS/MPN: nuclear events -epigenetics, spliceosomes and transcription factorsMutations in genes encoding epigenetic regulators are common in MDS/MPN. [32][33][34][35] The most frequently mutated genes are TET2 and ASXL1, followed by SRSF2, IDH1/2, EZH2, SUZ12, EED and UTX. 36 The interaction between epigenetic mutations is complex, and apart from the general mutual exclusivity of TET2 and IDH1/2 mutations, no clear patterns have emerged. 37,38 Mutations in elements involved in the recognition and processing of 3'-mRNA splice sites are also common in MDS/MPN. 39 Around 50% of CMML patients have mutations involving SRSF2, with a further 20% exhibiting mutations in other splicing complex genes (SF3B1, U2AF35, U2AF65 and SF3A1). 34,35,40,41 In addition, SF3B1 mutations are present in 72% of patients with RARS-T. 42,43 These SF3B1 mutations are...

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Section: Novel Strategies and Future Clinical Trial Designs For The Tmentioning

confidence: 99%

An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms

et al. 2015

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“…Studies have demonstrated that most patients would consider research biopsies [9][10][11], suggesting that nonpatient factors might hinder biopsy accrual. One such nonpatient factor could be provider comfort level in approaching patients for biopsies.…”

Section: Introductionmentioning

confidence: 99%

Variation in the Attitudes of Medical Oncologists Toward Research Biopsies in Patients With Metastatic Breast Cancer

et al. 2015

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Background. Tissue from research biopsies provides access to insights into tumor biology. We aimed to determine medical oncologists' (MOs') attitudes toward research biopsies in patients with metastatic breast cancer (MBC). Materials and Methods. A total of 309 breast MOs from National Cancer Institute (NCI)-designated cancer centers were invited to complete a self-administered survey about their attitudes toward approaching patients for research purposeonly biopsies (RPOBs), performed as a standalone procedure, or additional biopsies, performed with a clinically indicated biopsy. The MOs were asked to predict what proportion of their MBC patients would consider undergoing research biopsies. Results. Of the 309 MOs, 221 (72%) responded. Of these 221 MOs, 30 were ineligible, leaving 191 eligible responders. Nearly all the MOs reported they were comfortable approaching patients regarding research biopsies of blood or skin. One

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Patient attitudes towards undergoing additional breast biopsy for research

Naim¹,

Ballinger²,

Rombach³

et al. 2013

The Breast

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Patient willingness to undergo pharmacodynamic and pharmacokinetic tests in early phase oncology trials

Cited by 4 publications

References 23 publications

An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms

An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms

Variation in the Attitudes of Medical Oncologists Toward Research Biopsies in Patients With Metastatic Breast Cancer

Patient attitudes towards undergoing additional breast biopsy for research

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