Repurposing a psychoactive drug for children with cancer: p27Kip1-dependent inhibition of metastatic neuroblastomas by Prozac

Bibbò, Sandra; Lamolinara, Alessia; Capone, Emily; Purgato, Stefania; Tsakaneli, Alexia; Panella, Valeria; Sallese, Michele; Rossi, Cosmo; Ciufici, Paolo; Nieddu, Valentina; Laurenzi, Vincenzo De; Iezzi, Manuela; Perini, Giovanni; Sala, Gianluca; Sala, Arturo

doi:10.1038/s41389-019-0186-3

Cited by 8 publications

(4 citation statements)

References 27 publications

(27 reference statements)

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“…Spreading efficiency (i.e. % of animals producing metastatic lesions after intravenous cell injection) and timing (number of days after injection needed for ex-vivo detection of metastatic lesions by H&E staining) were established to select the appropriate starting points for treatment, as described [ 35 , 36 ]. A schematic representation of the experimental setting is shown in Figure 5 A.…”

Section: Resultsmentioning

confidence: 99%

Targeting Vesicular LGALS3BP by an Antibody-Drug Conjugate as Novel Therapeutic Strategy for Neuroblastoma

Capone

Lamolinara

Pastorino

et al. 2020

Cancers

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Neuroblastoma is the most common extra-cranial solid tumor in infants and children, which accounts for approximately 15% of all cancer-related deaths in the pediatric population. New therapeutic modalities are urgently needed. Antibody-Drug Conjugates (ADC)s-based therapy has been proposed as potential strategy to treat this pediatric malignancy. LGALS3BP is a highly glycosylated protein involved in tumor growth and progression. Studies have shown that LGALS3BP is enriched in extracellular vesicles (EV)s derived by most neuroblastoma cells, where it plays a critical role in preparing a favorable tumor microenvironment (TME) through direct cross talk between cancer and stroma cells. Here, we describe the development of a non-internalizing LGALS3BP ADC, named 1959-sss/DM3, which selectively targets LGALS3BP expressing neuroblastoma. 1959-sss/DM3 mediated potent therapeutic activity in different types of neuroblastoma models. Notably, we found that treatments were well tolerated at efficacious doses that were fully curative. These results offer preclinical proof-of-concept for an ADC targeting exosomal LGALS3BP approach for neuroblastomas.

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Section: Resultsmentioning

confidence: 99%

Targeting Vesicular LGALS3BP by an Antibody-Drug Conjugate as Novel Therapeutic Strategy for Neuroblastoma

Capone

Lamolinara

Pastorino

et al. 2020

Cancers

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“…Furthermore, small doses of FLX reduced the invasiveness and metastasis of neuroblastoma cells. This effect was further validated in a xenograft mice model [58].…”

Section: Flx In Brain Tumorsmentioning

confidence: 80%

Beyond Psychotropic: Repurposing of Fluoxetine Toward Cancer Management and Its Molecular Mechanisms

Kadasah,

Alqahtani,

Radwan

2024

Preprint

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Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antide-pressants (TCAs) were studied for their potential application in different diseases es-pecially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from SSRIs class for the treatment of several neuropsychiatric disorders with a favourable safety profile. FLX exhibited different oncolytic effects via mechanisms dis-tinct from its main serotonergic activity. Taking advantage of its ability to rapidly pen-etrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers highlighting the multifaceted activities of FLX and its ability to interrupt cancer prolif-eration via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX on car-riers to enhance its safety and efficacy on cancer cells. This is the first review article ex-tensively summarizing all previous FLX repurposing studies for the management of cancer.

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“…Furthermore, small doses of FLX reduced the invasiveness and metastasis of neuroblastoma cells. This effect was further validated in a xenograft mice model [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy

Kadasah,

Alqahtani,

Alkhammash

et al. 2024

IJMS

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Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood–brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.

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Repurposing a psychoactive drug for children with cancer: p27Kip1-dependent inhibition of metastatic neuroblastomas by Prozac

Cited by 8 publications

References 27 publications

Targeting Vesicular LGALS3BP by an Antibody-Drug Conjugate as Novel Therapeutic Strategy for Neuroblastoma

Targeting Vesicular LGALS3BP by an Antibody-Drug Conjugate as Novel Therapeutic Strategy for Neuroblastoma

Beyond Psychotropic: Repurposing of Fluoxetine Toward Cancer Management and Its Molecular Mechanisms

Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy

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