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A Drug Repurposing Screen Identifies Fludarabine Phosphate as a Potential Therapeutic Agent for N-MYC Overexpressing Neuroendocrine Prostate Cancers

ABSTRACT: A Drug Repurposing Screen Identifies Fludarabine Phosphate as a Potential Therapeutic Agent for N-MYC Overexpressing Neuroendocrine Prostate Cancers

PROVIDER: PRJNA750746 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15296015_1.fastq.gz	Fastqsanger.gz
	SRR15296015_2.fastq.gz	Fastqsanger.gz
	SRR15296016_1.fastq.gz	Fastqsanger.gz
	SRR15296016_2.fastq.gz	Fastqsanger.gz
	SRR15296017_1.fastq.gz	Fastqsanger.gz

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A Drug Repurposing Screen Identifies Fludarabine Phosphate as a Potential Therapeutic Agent for N-MYC Overexpressing Neuroendocrine Prostate Cancers

Project description:Neuroendocrine prostate cancer (NEPC) represents a highly aggressive form of prostate tumors. NEPC results from trans-differentiated castration-resistant prostate cancer (CRPC) with increasing evidence indicating that the incidence of NEPC often results from the adaptive response to androgen deprivation therapy. Recent studies have shown that a subset of NEPC exhibits overexpression of the MYCN oncogene along with the loss of tumor suppressing TP53 and RB1 activities. N-MYC is structurally disordered with no binding pockets available on its surface and so far, no clinically approved drug is available. We adopted a drug-repurposing strategy, screened ~1800 drug molecules and identified Fludarabine Phosphate to preferentially inhibit proliferation of N-MYC overexpressing NEPC cells by inducing ROS. We also show that Fludarabine phosphate affects N-MYC protein levels and N-MYC transcriptional targets in NEPC cells. Moreover, enhanced ROS production destabilizes N-MYC protein by inhibiting AKT signaling and is responsible for the reduced survival of NEPC cells and tumors. Our results indicate that increasing ROS production by administration of Fludarabine Phosphate may represent an effective treatment option for patients with N-MYC overexpressing NEPC tumors.

2022-07-20 | GSE181119 | GEO

A Drug Repurposing Screen Identifies Fludarabine Phosphate as a Potential Therapeutic Agent for N-MYC Overexpressing Neuroendocrine Prostate Cancers.

Project description:Neuroendocrine prostate cancer (NEPC) represents a highly aggressive form of prostate tumors. NEPC results from trans-differentiated castration-resistant prostate cancer (CRPC) with increasing evidence indicating that the incidence of NEPC often results from the adaptive response to androgen deprivation therapy. Recent studies have shown that a subset of NEPC exhibits overexpression of the MYCN oncogene along with the loss of tumor suppressing TP53 and RB1 activities. N-MYC is structurally disordered with no binding pockets available on its surface and so far, no clinically approved drug is available. We adopted a drug-repurposing strategy, screened ~1800 drug molecules, and identified fludarabine phosphate to preferentially inhibit the proliferation of N-MYC overexpressing NEPC cells by inducing reactive oxygen species (ROS). We also show that fludarabine phosphate affects N-MYC protein levels and N-MYC transcriptional targets in NEPC cells. Moreover, enhanced ROS production destabilizes N-MYC protein by inhibiting AKT signaling and is responsible for the reduced survival of NEPC cells and tumors. Our results indicate that increasing ROS production by the administration of fludarabine phosphate may represent an effective treatment option for patients with N-MYC overexpressing NEPC tumors.

| S-EPMC9317991 | biostudies-literature

Methoxyamine and Fludarabine Phosphate in Treating Patients With Relapsed or Refractory Hematologic Malignancies

Project description:This phase I trial is studying the side effects and best dose of methoxyamine when given together with fludarabine phosphate in treating patients with relapsed or refractory hematologic malignancies. Drugs used in chemotherapy, such as methoxyamine and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving methoxyamine together with fludarabine phosphate may kill more cancer cells.

| 2129878 | ecrin-mdr-crc

Treated Blood Cells, Cyclophosphamide, Fludarabine Phosphate, and Aldesleukin in Treating Patients With Cancer

Project description:RATIONALE: Placing a gene into T cells may improve the body’s ability to recognize cancer cells and build an immune response to fight cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop cancer cells from growing. Giving specially treated T cells together with cyclophosphamide, fludarabine phosphate, and aldesleukin may kill more tumor cells. PURPOSE: This phase I clinical trial is studying the side effects and best dose of treated T cells when given together with cyclophosphamide, fludarabine phosphate, and aldesleukin in treating patients with cancer.

| 2095938 | ecrin-mdr-crc

High-throughput Drug Screening Identifies Fluoxetine as a Potential Therapeutic Agent for Neuroendocrine Prostate Cancer

Project description:Here, we performed a high-throughput drug screening and identified fluoxetine, originally an FDA-approved antidepressant, as candidate therapeutic agent for NEPC. In vitro experiments revealed that fluoxetine effectively curbed the neuroendocrine differentiation and inhibited the cell viability by targeting the AKT pathway. Altogether, this work repurposed fluoxetine for antitumor application, and supported its clinical development for NEPC therapy, which may provide a promising therapeutic strategy.

2023-04-05 | GSE224715 | GEO

Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

Project description:This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient’s immune system from rejecting the donor’s stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient’s bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body’s normal cells. Giving total-body irradiation together with fludarabine phosphate, cyclosporine, and mycophenolate mofetil before transplant may stop this from happening.

| 2006050 | ecrin-mdr-crc

High-throughput Drug Screening Identifies Fluoxetine as a Potential Therapeutic Agent for Neuroendocrine Prostate Cancer

Project description:High-throughput Drug Screening Identifies Fluoxetine as a Potential Therapeutic Agent for Neuroendocrine Prostate Cancer

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High-throughput Drug Screening Identifies Ketotifen as a Potential Therapeutic Agent for Neuroendocrine Prostate Cancer

Project description:High-throughput Drug Screening Identifies Ketotifen as a Potential Therapeutic Agent for Neuroendocrine Prostate Cancer

| PRJNA933562 | ENA

Repurposing of the anti-malarial agent tafenoquine to combat MRSA

Project description:Tafenoquine , an anti-malarial agent, exhibited satisfactory antimicrobial efficacy against Staphylococcus aureus and its highly resistant phenotypes of biofilm and persister cells. Proteomic analysis of Staphylococcus aureus after treated with Tafenoquine was used to explore its underlying mechanisms.

2023-10-12 | PXD046080 |

Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

Project description:This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and donor stem cell transplant followed by cyclosporine, mycophenolate mofetil, and donor lymphocyte infusion in treating patients with hematopoietic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and total body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also keep the patient’s immune response from rejecting the donor’s stem cells. The donated stem cells may replace the patient’s immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor’s T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body’s normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

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