FY20 SBIR PHASE I TOPIC #400 - AMBAY RADI-SENSE: NON-INVASIVE, NOVEL TEST TO MONITOR BIOLOGICAL RESPONSE TO RADIOTHERAPY

放射治疗是前列腺癌的主要治疗方式，前列腺癌是男性最常见的恶性肿瘤，也是男性癌症相关死亡的第二大原因。尽管放射治疗在治疗器官受限/局限性晚期前列腺癌方面具有治愈潜力，但50%的患者经历了疾病的复发。目前的治疗方法是用“一刀切”的疗法治疗患者，但未能取得良好的效果。这项建议的目标是开发一种基于非侵入性(人血清)生物标记物(S)的测试--“放射感”，以实现放射治疗的个性化，从而指导临床医生为患者开发新的治疗方案。将通过监测导致放射治疗失败的细胞途径基因表达的变化来分析患者对放射治疗的反应。拟议的方法将(I)彻底改变目前衡量肿瘤大小变化的临床标准，以评估放射治疗的反应；(Ii)帮助设计有效的治疗方案，而不需要活组织检查/连续活检；(Iii)能够在放射治疗之前、期间和之后进行监测和采样；(Iv)将能够在治疗的早期阶段对高危患者进行适当的替代治疗，并使不太敏感的患者的肿瘤剂量增加；(V)引入将其他方式(例如免疫治疗、分子靶向治疗)与放射治疗结合使用的可能性。

Radiotherapy is a major curative treatment modality for prostate cancer, the most common malignancy and the second-leading cause of cancer-related death in men. Despite the curative potential of radiotherapy in treating organ-confined/localized advanced prostate cancer, 50% of the patients experience recurrence of the disease. The current approach, treating patients with "one-size-fits-all" therapy, has failed to deliver favorable results. The goal of this proposal is to develop a non-invasive (human serum) biomarker(s) based test, “RADI-Sense” to personalize radiotherapy, which can guide clinicians to develop new therapeutic regimes for patients. The patients’ response to radiotherapy will be analyzed by monitoring the changes in the expression of genes from cellular pathways leading to failure of radiotherapy. The proposed approach will (i) radically transform the current clinical standard of measuring changes in tumor size to assess response to radiotherapy; (ii) aid in designing effective treatment regimens without the need of biopsy/serial biopsies; (iii) enable monitoring and sampling prior to, during and after radiation treatment; (iv) will enable suitable alternative treatments to high-risk patients and dose escalation to tumors in less sensitive patients during early phases of treatment; (v) introduce the possibility of using other modalities (e.g. immunotherapy, molecular targeted therapy) in combination with radiotherapy.