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Principal Investigator: Felix Yi-Chung Feng
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $618,546
Funding agency: National Cancer Institute
Project Abstract
Castrate resistant prostate cancer is a uniformly lethal disease and, although there have been a number of
new therapeutic agents approved, there is still a large need for more effective treatments in this patient
population. In this proposal, we will study a radioligand therapy (RLT) that targets the prostate specific
membrane antigen (PSMA), a molecule that is expressed on the majority of prostate cancer cells. In multiple
small studies, PSMA RLT has shown to have remarkable efficacy in heavily pretreated patients, with over 40%
of patients having decreased PSA of over 50%. PSMA RLT relies on two basic premises: targeting the
radiation to PSMA and the radiosensitivity of the tissue to the deposited radiation. First, we will understand
how PSMA expression is regulated, allowing us to pharmacologically target cancer cells to increase their
PSMA expression. Second, we will understand whether tumors respond because of intrinsic sensitivity to
radiation or high doses of deposited radiation. This knowledge will be critical to determine if patients need
higher expression of PSMA or increased tumor cell sensitivity in order to improve the response to this therapy.
We will test treatments capable of increasing the sensitivity of tumors to radiation as well as potential therapies
that can increase expression of PSMA. This work will be used to inform the development of a clinical trial that
will involve PSMA RLT and a co-administered therapy to increase its already promising efficacy.
Terms: <After Care><After-Treatment><Aftercare><Animal Model><Animal Models and Related Studies><Biological Markers><Biopsy><Blood><Blood Reticuloendothelial System><Body Tissues><CRISPR><CRISPR editing screen><CRISPR screen><CRISPR-based screen><CRISPR/Cas system><CRISPR/Cas9 screen><Cell Culture Techniques><Cell Line><Cell surface><CellLine><Clinical><Clinical Trials><Clustered Regularly Interspaced Short Palindromic Repeats><Computational Biology><Data Set><Deposit><Deposition><Development><Disease><Disorder><Dose><FOLH><FOLH1><FOLH1 gene><Folate Hydrolase 1><GCP2><Gene Expression><Genes><Genome><Genomics><Glutamate Carboxypeptidase II><Heterogeneity><Image><Intervention><Intervention Strategies><Knowledge><Lesion><Lutetium><Malignant Cell><Measures><Mediating><Modeling><Molecular><N-Acetylated Alpha-Linked Acidic Dipeptidase 1><NAALAD1><NAALADase I><Neoplasm Circulating Cells><Network Analysis><Oligonucleotide Array><Oligonucleotide Microarrays><PDX model><PET><PET Scan><PET imaging><PETSCAN><PETT><PSA level><PSM><PSMA><Pathway Analysis><Pathway interactions><Patient Selection><Patient derived xenograft><Patients><Phase 3 Clinical Trials><Phase III Clinical Trials><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prostate-Specific Membrane Antigen><Publishing><Rad.-PET><Radiation><Radiation Sensitivity><Radiation Tolerance><Radioactive Isotopes><Radiography><Radioisotopes><Radionuclides><Radiosensitivity><Randomized><Receptor Protein><Roentgenography><SPECT><SPECT imaging><Sampling><Serology><Single-Photon Emission-Computed Radionuclide Tomography><Strains Cell Lines><System><Testing><Therapeutic><Therapeutic Agents><Time><Tissues><Toxic effect><Toxicities><Treatment Efficacy><Tumor Cell><Work><absorption><androgen independent prostate cancer><androgen indifferent prostate cancer><androgen insensitive prostate cancer><androgen resistance in prostate cancer><androgen resistant prostate cancer><bio-markers><biologic marker><biomarker><cancer cell><castration resistant CaP><castration resistant PCa><castration resistant prostate cancer><cell culture><cell cultures><circulating neoplastic cell><circulating tumor cell><clustered regularly interspaced short palindromic repeats screen><computer biology><cultured cell line><developmental><diagnostic ability><diagnostic capability><diagnostic power><diagnostic utility><diagnostic value><dosimetry><effective therapy><effective treatment><genomic biomarker><genomic data><genomic data-set><genomic dataset><genomic marker><global gene expression><global transcription profile><hormone refractory prostate cancer><imaging><imaging biomarker><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><improved><intervention efficacy><interventional strategy><irradiation response><model of animal><neoplastic cell><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><pathway><patient derived xenograft model><patient population><pharmacologic><phase 3 trial><phase III protocol><phase III trial><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><post treatment><predict responsiveness><predicting response><prospective><prostate cancer cell><prostate cancer resistant to androgen><prostate specific antigen level><prostate tumor cell><radiation response><radio-sensitivity><radioligand><radiologic imaging><radiological imaging><radiosensitive><randomisation><randomization><randomly assigned><receptor><response><response to radiation><response to therapy><response to treatment><single photon emission computed tomography><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic efficacy><therapeutic response><therapy efficacy><therapy response><transcriptome><transcriptomics><treatment response><treatment responsiveness><tumor><uptake>