Exploring Precision Oncology: From Gene Fusions to lncRNAs

探索精准肿瘤学：从基因融合到 lncRNA

• 批准号: 10219190
• 负责人: ARUL M CHINNAIYAN
• 金额: $ 92.87万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10219190
• 关键词: Achievement; Advanced Malignant Neoplasm; Antisense Oligonucleotides; Area; Award; Biological; Biological Markers; Cancer Intervention; Cancer Patient; Clinical; Communities; Data; Development; Diagnosis; Diagnostic; Disseminated Malignant Neoplasm; ERG gene; Foundations; Gene Fusion; Goals; Human; Individual; Malignant Neoplasms; Malignant neoplasm of prostate; Mission; Modeling; Molecular; Molecular Target; PSA level; Pathogenesis; Patients; Peptides; Prognosis; Prostate; Reporting; Research; Research Personnel; Resources; Role; Sampling; Screening for Prostate Cancer; Serum; TMPRSS2 gene; Therapeutic Intervention; Untranslated RNA; Urine; Validation; Work; bioinformatics resource; cancer type; clinical sequencing; disease diagnosis; efficacious treatment; experience; inhibitor/antagonist; knowledge base; novel marker; peptidomimetics; precision medicine; precision oncology; prognostic; programs; research clinical testing; single cell sequencing; targeted treatment; therapeutic development; therapeutic target; transcriptome; transcriptomics; translational cancer research; tumor progression

Project Summary / Abstract The potential of precision medicine to benefit the lives of cancer patients continues to emerge. The mission of the Chinnaiyan lab is to advance the field of precision oncology, and we aim to achieve this through the discovery and development of molecular targets that will aid in diagnosis, prognosis, or therapeutic intervention of cancers. Over the past several years, we have made a number of significant advancements in these areas. One of these landmark studies found that TMPRSS2-ETS gene fusions exist in the majority of prostate cancers. This discovery led to our development of a non-invasive clinical test (Mi-Prostate Score, MiPS) that combines analysis of urine levels of TMPRSS2-ERG and the long non-coding RNA (lncRNA) PCA3 with serum levels of PSA to detect prostate cancers. Due to its subsequently established roles in prostate cancer pathogenesis, we also reported on the development of peptidomimetic inhibitors (ERG inhibitory peptides, EIPs) of the ERG gene fusion product. A monumental achievement in the field of precision oncology has also been establishment of our comprehensive sequencing program for advanced cancer patients, called Mi-Oncoseq. Mi-Oncoseq has become a model for integrative clinical sequencing and generated several pivotal findings, including our recent report on the integrative sequencing analysis of metastatic cancers. Data from our sequencing program were also included in our report of the lncRNA landscape of the human transcriptome. Studies of individual lncRNAs have additionally emerged in our lab, such as validation of SChLAP1 as a marker for aggressive prostate cancer. This brief description of selected achievements highlights our commitment to advancing precision oncology and our vast foundational experience in this arena. Through the NCI Outstanding Investigator Award, we propose to continue these lines of research to further explore the diagnostic potential of precision oncology, therapeutic targeting of identified markers, and roles of nominated targets in cancer development. The future research program centered on diagnostic potential will include such initiatives as creation of new bioinformatic resources (e.g. “Mi-PANDA”, a compendia of transcriptomic data), high throughput single cell sequencing analysis of patient samples, and creation of cancer-specific lncRNA panels for use with non-invasive clinical isolates. Therapeutic targeting will be explored through the use of antisense oligos to lncRNAs and studies on the efficacy of peptidomimetics for gene fusions and “undruggable” targets. These avenues of research will provide impetus for studying the roles of selected noteworthy targets in cancer development. In particular, we have already discovered two lncRNAs, ARlnc1 and THOR1, which appear to be involved in cancer progression. Overall, this ambitious research program will advance the field of precision oncology by providing new community resources, identifying novel biomarkers, exploring the therapeutic targeting of nominated molecular players, and adding to the knowledge-base of cancer development mechanisms, particularly those of lncRNAs. Importantly, this award and the proposed work would assist our lab in its mission to remain a leader in the field of precision oncology.

项目摘要/摘要