20 years of precision medicine in oncology

Lancet, The

doi:10.1016/s0140-6736(21)01099-0

Cited by 28 publications

(10 citation statements)

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“…Due to the high morbidity associated with the current clinical management of OSCC [ 1 , 3 ], it is essential to identify putative oncogenes driving carcinogenesis that may also be used as prognostic factors and targeted for therapeutic benefit. Recently, the advancement of high-throughput multi-omic technologies has facilitated comprehensive molecular profiling of tumour samples to identify drivers of oncogenesis and progression, which may lead to the development of precision oncotherapeutics [ 32 , 33 ]. Here, we analysed OSCC genomes and transcriptomes to identify candidate driver oncogenes on the chromosomal cytobands 3q22-3q29, which is frequently amplified in squamous cell carcinomas [ 14 – 17 ].…”

Section: Discussionmentioning

confidence: 99%

NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma

et al. 2023

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There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.

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Section: Discussionmentioning

confidence: 99%

NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma

et al. 2023

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“…PM allows taking advantage of patient heterogeneity, which is often viewed as a drawback in the context of evidence-based medicine. 2,5 To date, PM is most commonly applied in the field of oncology, 4,[6][7][8] and is characterized by developing pairs of companion diagnostic-targeted cancer medicines. 9 Multiple stakeholders are involved in the pathway from testing to targeted treatments, including patients themselves and patient organizations, treating clinicians and healthcare providers (HCPs), clinical and academic researchers, policymakers, payers, regulators, and industry representatives.…”

Section: Introductionmentioning

confidence: 99%

Stakeholders' expectations of precision medicine: A qualitative study to identify areas of (mis)alignment

Knott,

Creeden,

Horbach

et al. 2023

Health Science Reports

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Background and AimsTo sustainably address challenges in implementing precision medicine (PM), coordinated efforts of different stakeholders are required. Understanding their expectations represents a first key step toward aligning on future actions and strategies. Here, we aimed to explore the expectations of different stakeholders from themselves and each other regarding PM.MethodsThis collaborative qualitative study was initiated by the global multistakeholder consortium From Testing to Targeted Treatments (FT3). Structured interviews were conducted with participants from five stakeholder groups: patients/patient advocates, healthcare providers (HCPs), researchers, policymakers/regulators/payers and industry representatives. A broad reach across geography, roles, experiences, and disease areas was sought. Results were analyzed by grounded theory methodology.ResultsAll stakeholders stated that optimal implementation of PM can only be achieved through collaboration; industry representatives were the biggest promoters of collaboration. Stakeholders agreed that PM should be implemented focusing on the patient's best interest; HCPs were seen as important gatekeepers for PM by interacting directly with patients, and policymakers/payers were perceived as the most important drivers of access to PM. Areas of misalignment included the role of industry in clinical trial design and in access to PM (perceived as important by patients, HCPs and policymakers but not by industry representatives), and the stakeholders responsible for elaborating guidelines on PM use (patients indicated policymakers, while researchers indicated themselves). Priorities for optimal PM implementation and suggested actions included the need for enhancing high‐level policy focus, improving genomic literacy, optimizing the health technology assessment for PM, advocating for equitable access, promoting collaboration between industry and other stakeholder groups and development of reliable research standards.ConclusionStakeholder expectations revealed in this study suggested that no stakeholder group can drive change on its own; a global, multistakeholder collaborative approach that brings together current programs and best practices to support universal access to PM is needed.

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“…Although precision dosing has been widely implemented in oncology based on the genetic and molecular characterization of the target tissue and individual patient [ 11 ], this concept is relatively new in the field of antithrombotic drugs. High intra- and inter-individual variability in drug response that may impact efficacy and safety outcomes, large number of patients exposed to the drug or largely under-represented patient groups, and availability of a validated pharmacokinetic/pharmacodynamic biomarker are relevant aspects requiring a precision dosing approach [ 12 ].…”

Section: Introductionmentioning

confidence: 99%