Global Implementation of Precision Oncology.
Ontology highlight
ABSTRACT:
SUBMITTER: Yam C
PROVIDER: S-EPMC8232074 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:We introduce OncoLoop, a highly-generalizable, precision medicine framework to triangulate between available mouse models, human tumors, and large-scale drug perturbational assays with in vivo validation to predict personalized treatment
2022-10-31 | GSE186566 | GEO
Project description:The advent of molecular diagnostics and the rising number of targeted therapies have facilitated development of precision oncology for cancer patients. In order to demonstrate its impact for patients with metastatic breast cancer (mBC), we initiated a Molecular Tumor Board (MTB) to provide treatment recommendations for mBC patients who had disease progression under standard treatment. NGS (next generation sequencing) was carried out using the Oncomine multi-gene panel testing system (Ion Torrent). The MTB reviewed molecular diagnostics' results, relevant tumor characteristics, patient's course of disease and made personalized treatment and/or diagnostic recommendations for each patient. From May 2017 to December 2019, 100 mBC patients were discussed by the local MTB. A total 72% of the mBC tumors had at least one molecular alteration (median 2 per case, range: 1 to 6). The most frequent genetic changes were found in the following genes: PIK3CA (19%) and TP53 (17%). The MTB rated 53% of these alterations as actionable and treatment recommendations were made accordingly for 49 (49%) patients. Sixteen patients (16%) underwent the suggested therapy. Nine out of sixteen patients (56%; 9% of all) experienced a clinical benefit with a progression-free survival ratio ≥ 1.3. Personalized targeted therapy recommendations resulting from MTB case discussions could provide substantial benefits for patients with mBC and should be implemented for all suitable patients.
| S-EPMC8074310 | biostudies-literature
Project description:Over the last few decades, molecularly targeted agents have been used for the treatment of metastatic colorectal cancer. They have made remarkable contributions to prolonging the lives of patients. The emergence of several biomarkers and their introduction to the clinic have also aided in guiding such treatment. Recently, next-generation sequencing (NGS) has enabled clinicians to identify these biomarkers more easily and reliably. However, there is considerable uncertainty in interpreting and implementing the vast amount of information from NGS. The clinical relevance of biomarkers other than NGS are also subjects of debate. This review covers controversial issues and recent findings on such therapeutics and their molecular targets, including VEGF, EGFR, BRAF, HER2, RAS, actionable fusions, Wnt pathway and microsatellite instability for comprehensive understanding of obstacles on the road to precision oncology in metastatic colorectal cancer.
| S-EPMC7078672 | biostudies-literature
Project description:Radiation therapy is a critical component in the curative management of many solid tumor types, and advances in radiation delivery techniques during the past decade have led to improved disease control and quality of life for patients. During the same period, remarkable advances have also been made in understanding the genomic landscape of tumors; however, treatment decisions in radiation oncology continue to depend primarily on clinical and histopathologic characteristics rather than on the genetic features of the tumor or the patient. With the development of novel genomic techniques and their increasing use in clinical practice, radiation oncology is uniquely positioned to leverage these advances to identify novel biomarkers that could inform radiation dose, field, and the use of concurrent systemic agents. Here, we summarize efforts to use genomic techniques to guide radiation decisions, and we highlight some of the current opportunities and challenges that exist in attempting to apply precision oncology principles in radiation oncology.
| S-EPMC7446508 | biostudies-literature
Project description:Epigenetic alterations such as DNA methylation defects and aberrant covalent histone modifications occur within all cancers and are selected for throughout the natural history of tumor formation, with changes being detectable in early onset, progression, and ultimately recurrence and metastasis. The ascertainment and use of these marks to identify at-risk patient populations, refine diagnostic criteria, and provide prognostic and predictive factors to guide treatment decisions are of growing clinical relevance. Furthermore, the targetable nature of epigenetic modifications provides a unique opportunity to alter treatment paradigms and provide new therapeutic options for patients whose malignancies possess these aberrant epigenetic modifications, paving the way for new and personalized medicine. DNA methylation has proven to be of significant clinical utility for its stability and relative ease of testing. The intent of this review is to elaborate upon well-supported examples of epigenetic precision medicine and how the field is moving forward, primarily in the context of aberrant DNA methylation.
| S-EPMC5708865 | biostudies-literature
Project description:Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.
| S-EPMC6119176 | biostudies-other
Project description:In recent years, precision medical detection techniques experienced a rapid transformation from low-throughput to high-throughput genomic sequencing, from multicell promiscuous detection to single-cell precision sequencing. The emergence of liquid biopsy technology has compensated for the many limitations of tissue biopsy, leading to a tremendous transformation in precision detection. Precision detection techniques contribute to monitoring disease development more closely, evaluating therapeutic effects more scientifically, and developing new targets and new drugs. In the future, the role of precision detection and the joint detection in epigenetics, rare gene detection, individualized targeted therapy, and multigene targeted drug combination therapy should be extensively explored. This article reviews the changes in precision medical detection technology in the era of precision medicine, as well as the development, clinical application, and future challenges of liquid biopsy.
| S-EPMC7368234 | biostudies-literature
Project description:<p>Shankha Satpathy, Eric J. Jaehnig, et al., <a href="https://www.nature.com/articles/s41467-020-14381-2" target="_blank">Nature Communications volume 11, Article number: 532 (2020)</a></p><p>Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48-72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsy-scale warrants further investigation.<br><br><em>Genomic Data</em> for samples in the Microscaled Proteogenomic Methods Publication are available from the NIH Database of Genotypes and Phenotypes (dbGaP), Study Accession: phs001907.v1.p1, <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001907.v1.p1" target="_blank">here</a></p>
<ul><li>Dataset imported into MassIVE from <a href="https://cptac-data-portal.georgetown.edu/study-summary/S051">https://cptac-data-portal.georgetown.edu/study-summary/S051</a> on 06/02/21</li></ul>
2021-06-02 | MSV000087566 | MassIVE
Project description:With the widespread adoption of molecular profiling in clinical oncology practice, many physicians are faced with making therapeutic decisions based upon isolated genomic alterations. For example, epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are effective in EGFR-mutant non-small cell lung cancers (NSCLC) while anti-EGFR monoclonal antibodies are ineffective in Ras-mutant colorectal cancers. The matching of mutations with drugs aimed at their respective gene products represents the current state of "precision" oncology. Despite the great expectations of this approach, only a fraction of cancers responds to 'targeted' interventions, and many early responders will ultimately develop resistance to these agents. The underwhelming success of mutation-driven therapies across all cancer types is not due to an inability to detect genetic changes in tumors; rather a deficit in functional insight into the genomic alterations that give rise to each cancer. The Achilles heel of precision oncology thus remains the lack of a robust functional understanding of an individual cancer genome that then allows prediction of the best therapy and resultant outcome for that patient. Current practice focuses on one 'actionable' mutation at a time, while solid cancers typically possess many mutations that involve different cellular sub-populations within a tumor. No method or platform currently exists to guide the interpretation of these complex data, nor to accurately predict response to treatment. This problem is particularly germane to primary liver cancers (PLC), for which only a handful of targeted therapies have been introduced. Here, we will review strategies aimed at overcoming some of these challenges in precision oncology, using liver cancer as an example.
| S-EPMC6068329 | biostudies-literature
Project description:Current efforts in precision oncology largely focus on the benefit of genomics-guided therapy. Yet, advances in sequencing techniques provide an unprecedented view of the complex genetic and nongenetic heterogeneity within individual tumors. Herein, we outline the benefits of integrating genomic and transcriptomic analyses for advanced precision oncology. We summarize relevant computational approaches to detect novel drivers and genetic vulnerabilities, suitable for therapeutic exploration. Clinically relevant platforms to functionally test predicted drugs/drug combinations for individual patients are reviewed. Finally, we highlight the technological advances in single cell analysis of tumor specimens. These may ultimately lead to the development of next-generation cancer drugs, capable of tackling the hurdles imposed by genetic and phenotypic heterogeneity on current anticancer therapies.
| S-EPMC5718207 | biostudies-literature