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Repurposing systemic therapies to improve clinical outcomes in advanced basal cell cancer

重新利用全身疗法以改善晚期基底细胞癌的临床结果

基本信息

批准号：
10335186
负责人：
Kavita Yang Sarin
金额：
$ 17.36万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10335186
关键词：
Aftercare Allografting Alternative Therapies Basal Cell Cancer Basal cell carcinoma Bioinformatics Biopsy Biopsy Specimen CD8B1 gene Cancer Cell Growth Cancer cell line Clinical Clinical Trials Clinical Trials Design Coupled Cutaneous Data Development Development Plans Diagnosis Doctor of Medicine Doctor of Philosophy Experimental Models FDA approved Financial Support Future GLI gene GTP-Binding Proteins Geldanamycin Genetic Genetic Transcription Genomics Goals Grant Growth HDAC1 gene Histone Deacetylase Histone Deacetylase Inhibitor Human Immune Immunologics Immunotherapy In Vitro Investigation JAK1 gene Laboratories Malignant Neoplasms Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Molecular Mus Mutant Strains Mice Mutation Neoplasm Metastasis Oncology Oral Outcome PD-1 blockade PD-1 inhibitors Pathway interactions Patients Pharmaceutical Preparations Phase Phase II Clinical Trials Pre-Clinical Model Principal Investigator Prognosis Publications Regulation Research Research Personnel Resistance Role Sampling Sarin Signal Transduction Skin Cancer Skin Carcinoma Small Cell Carcinoma Systemic Therapy Therapeutic Thiazolidinediones Time Training Translational Research Tumor-Infiltrating Lymphocytes United States Universities Vorinostat anti-PD-L1 therapy base bench to bedside cancer cell cancer invasiveness career development checkpoint therapy clinical investigation data modeling exome sequencing experience improved improved outcome inhibitor loss of function loss of function mutation melanoma multidisciplinary new therapeutic target novel therapeutics open label pembrolizumab preclinical study professor programmed cell death ligand 1 rational design receptor response skills skin squamous cell carcinoma smoothened signaling pathway targeted treatment therapeutic candidate transcriptome sequencing transcriptomics translational scientist treatment group tumor tumorigenesis

项目摘要

REPURPOSING SYSTEMIC THERAPIES TO IMPROVE CLINICAL OUTCOMES IN ADVANCED BASAL CELL CANCER PROJECT SUMMARY This is an application for a K23 Mentored Patient-Oriented Research Career Development Award for Dr. Kavita Sarin, an Assistant Professor at Stanford University. Dr. Sarin is establishing herself as a translational investigator in cutaneous oncology, focused on developing rationally-designed molecular-based therapies for patients with non-melanoma skin cancer. The K23 Award will provide Dr. Sarin the support needed to achieve this goal by: 1) enabling her to obtain training in advanced bioinformatics, translational research, clinical trial design, and cutaneous oncology through research, mentorship and didactics; 2) providing protected time to pursue her research goals under the guidance of an experienced multidisciplinary team of mentors; and 3) enabling publications and speaking opportunities to gain recognition in the field of cutaneous oncology. Dr. Sarin has assembled a team of mentors and collaborators with expertise in translational laboratory investigation and clinical trials in advanced basal cell cancer (Anthony Oro M.D. Ph.D., Jean Tang M.D. Ph.D., Ervin Epstein M.D. Ph.D., Anne Chang M.D. Ph.D.) and applied bioinformatics (Howard Chang M.D. Ph.D., Marina Sirota Ph.D.). With her mentorship team, Dr. Sarin has developed a comprehensive career development plan to transition from a mentored investigator to an independent translational investigator in cutaneous oncology. Dr. Sarin’s research plan aims to investigate new targeted and immune-checkpoint therapies for the treatment of advanced basal cell cancer (BCC). Using a bioinformatics-based drug-repositioning screen, she identified the histone deacetylase inhibitor, vorinostat, as a candidate therapeutic for advanced BCC. Subsequent preclinical studies demonstrated that vorinostat can suppress hedgehog signaling and BCC growth in BCC cell lines and tumor allografts. In Aim 1, Dr. Sarin will mechanistically interrogate the role of HDAC1 in Hh signaling and conduct a Phase 2 open-label clinical trial of vorinostat in 24 patients with advanced BCC. In Aim 2, Dr. Sarin will investigate genomic, transcriptomic, and immunologic correlates to PD-1 blockade in advanced basal cell cancer. Dr. Sarin has the full support of her mentors and Stanford University, who are providing guidance, samples, and financial support for the proposal. Successful completion of this proposal will allow Dr. Sarin to develop the multidisciplinary skills needed to be an independent principal investigator in the development of molecular-based therapeutics for skin cancer and will generate the preliminary data for a future R01 grant.

重新利用全身治疗来改善晚期基底细胞的临床结果

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intravital 3D visualization and segmentation of murine neural networks at micron resolution.

DOI：
10.1038/s41598-022-14450-0
发表时间：
2022-07-30
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Lautman, Ziv;Winetraub, Yonatan;Blacher, Eran;Yu, Caroline;Terem, Itamar;Chibukhchyan, Adelaida;Marshel, James H.;de la Zerda, Adam
通讯作者：
de la Zerda, Adam

Flexible method for generating needle-shaped beams and its application in optical coherence tomography.

DOI：
10.1364/optica.456894
发表时间：
2022-08-20
期刊：
Optica
影响因子：
10.4
作者：
通讯作者：

Status and Recommendations for Incorporating Biomarkers for Cutaneous Neurofibromas Into Clinical Research.

将皮肤神经纤维瘤生物标志物纳入临床研究的现状和建议。

DOI：
10.1212/wnl.0000000000012426
发表时间：
2021
期刊：
Neurology
影响因子：
9.9
作者：
Wallis,Deeann;Stemmer-Rachamimov,Anat;Adsit,Sarah;Korf,Bruce;Pichard,Dominique;Blakeley,Jaishri;Sarin,KavitaY;REiNSInternationalCollaboration
通讯作者：
REiNSInternationalCollaboration

Optical-resolution photoacoustic microscopy with a needle-shaped beam