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Molecular Biomarkers of Long-Term Response to Androgen Deprivation Therapy and Radiation in Prostate Cancer

前列腺癌雄激素剥夺疗法和放射长期反应的分子生物标志物

基本信息

批准号：
10366451
负责人：
Jingqin Luo
金额：
$ 67.35万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10366451
关键词：
Address Androgens Biological Assay Cancer Patient Clinical Data Diagnosis Disease Event Exposure to Face Freedom Gene Expression Profile Genes Genomics Goals Guidelines High-Throughput DNA Sequencing Local Therapy Localized Disease Malignant Neoplasms Malignant neoplasm of prostate National Comprehensive Cancer Network Operative Surgical Procedures PSA level Pathologic Patient Care Patient-Focused Outcomes Patients Pelvic lymph node group Performance Phase III Clinical Trials Positioning Attribute Postoperative Period Prognostic Marker Prostate Cancer therapy Prostatectomy Publishing Radiation Radiation Therapy Oncology Group Radiation therapy Radical Prostatectomy Randomized Recurrence Research Resources Retrospective cohort Sampling Technology Therapeutic Tissues United States Vertebral column androgen deprivation therapy arm biobank cancer recurrence clinical translation cohort disorder control follow-up high risk improved men molecular marker novel patient subsets personalized medicine phase III trial predicting response predictive marker predictive modeling predictive signature prognostic prospective prostate cancer risk randomized trial response serum PSA side effect standard care standard of care transcriptome transcriptome sequencing transcriptomics treatment strategy tumor

项目摘要

Of the 33,330 men who died from prostate cancer in United States last year, over 80% of these patients presented with localized disease. Thus, a majority of PCa patients are diagnosed at a potentially curable stage and are often treated with radical prostatectomy (RP). Following RP, patients with aggressive disease face the risk of prostate cancer recurrence, which manifests as persistently elevated or increasing serum PSA. While salvage radiation therapy (RT) represents a standard treatment option for post-surgical recurrences, it results in long-term disease control in only 30-40% of patients. Thus, the post-surgical recurrence state presents multiple opportunities to improve patient care by addressing three critical challenges: (1) determining which patients will benefit from the addition of androgen deprivation therapy (ADT), (2) identifying which patients treated with RT and ADT will require further treatment intensification, and (3) identifying the appropriate treatment intensification strategy for RT and ADT treated patients. Since androgen-directed therapies represent the backbone of treatment for PCa (that have progressed through local therapies) the RTOG 96-01 and RTOG 05-34 phase III clinical trials represent a unique resource of banked prostatectomy cohorts from patients that were randomized to the presence or absence of treatment with ADT. For patients whose clinical and pathologic features place them at highest risk of dying from PCa, these landmark trials have defined the standard of care by showing that the addition of ADT to RT resulted in significant improvements to patient survival compared to RT alone. This presents an unparalleled opportunity to develop and validate predictive and prognostic biomarkers addressing multiple unmet clinical needs throughout patient care following surgery. Aim 1 will focus on using high-throughput DNA and RNA sequencing to develop a predictive classifier for identifying which patients would benefit from ADT using patients from RTOG 96-01 and 05-34. In Aim 2 we will develop and validate a prognostic classifier that integrates genomic and clinicopathologic data for PCa patients treated with RT+ADT that may benefit from treatment intensification. Aim 3 will focus on identifying RT+ADT patients requiring treatment intensification that could benefit from receiving pelvic lymph node radiation therapy using patients from RTOG 05-34. The proposed study would have significant impact by developing and optimizing prognostic and predictive biomarkers that could have enormous potential for rapid clinical translation to personalize therapy and transform the management of PCa patients following surgery.

去年美国有33330名男性死于前列腺癌，超过80%的患者