Antidepressants with anti‐tumor potential in treating glioblastoma: A narrative review

Glioblastoma (GBM) remains one of the most difficult tumors to treat. The mean overall survival rate of 15 months and the 5-year survival rate of 5% have not significantly changed for almost 2 decades. Despite progress in understanding the pathophysiology of the disease, no new effective treatments to combine with radiation therapy after surgical tumor debulking have become available since the introduction of temozolomide in 1999. One of the main reasons for this is the scarcity of compounds that cross the blood–brain barrier (BBB) and reach the brain tumor tissue in therapeutically effective concentrations. In this review, we focus on the role of the BBB and its importance in developing brain tumor treatments. Moreover, we discuss drug repurposing, a drug discovery approach to identify potential effective candidates with optimal pharmacokinetic profiles for central nervous system (CNS) penetration and that allows rapid implementation in clinical trials. Additionally, we provide an overview of repurposed candidate drug currently being investigated in GBM at the preclinical and clinical levels. Finally, we highlight the importance of phase 0 trials to confirm tumor drug exposure and we discuss emerging drug delivery technologies as an alternative route to maximize therapeutic efficacy of repurposed candidate drug.

Section: Drug Repurposing For Glioblastomamentioning

confidence: 99%

Drug Repurposing, a Fast-Track Approach to Develop Effective Treatments for Glioblastoma

Ntafoulis

Koolen

Leenstra

et al. 2022

“…In turn, interleukin-6 contributes to supporting GBM progression via the autocrine pathway [ 206 ]. Generally, targeting 5-HT receptors is a type of potential way of treating GBM, functioning as reinforcement to chemotherapy [ 207 , 208 , 209 ].…”

Section: The Influence Of Neurotransmitters On Gbm and Potential Ther...mentioning

confidence: 99%

“…Following studies discovered that SSRIs suppress GBM cell proliferation in different ways. What is worth mentioning is that some FDA-approved antidepressants already reached favorable outcomes in clinical trials [ 208 , 210 ]. Considered as a more superior SSRI, escitalopram oxalate exhibits favorable tolerability.…”

Section: The Influence Of Neurotransmitters On Gbm and Potential Ther...mentioning

confidence: 99%

Neurotransmitters: Potential Targets in Glioblastoma

Huang

Chen

Liang

et al. 2022

For decades, glioblastoma multiforme (GBM), a type of the most lethal brain tumor, has remained a formidable challenge in terms of its treatment. Recently, many novel discoveries have underlined the regulatory roles of neurotransmitters in the microenvironment both physiologically and pathologically. By targeting the receptors synaptically or non-synaptically, neurotransmitters activate multiple signaling pathways. Significantly, many ligands acting on neurotransmitter receptors have shown great potential for inhibiting GBM growth and development, requiring further research. Here, we provide an overview of the most novel advances concerning the role of neurotransmitters in the normal neural and the GBM microenvironments, and discuss potential targeted drugs used for GBM treatment.

“…In fact, several in vitro and preclinical studies and reviews have evaluated the effect of antidepressants in tumors of the central nervous system. The review by Abadi et al suggested that the high occurrence rates of depression in glioblastoma multiforme patients, as well as the overlap of molecular and cellular mechanisms involved in the pathogenesis of these diseases, make antidepressants with antitumor effects an affordable strategy for the treatment of this tumor [93]. Some of the in vitro and preclinical studies go back to the end of the twentieth century, with the one reported by Richelson in 1978 being the earliest.…”

Section: Cancer Of Central Nervous Systemmentioning

confidence: 99%

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment

Asensi-Cantó

López-Abellán

Castillo-Guardiola

et al. 2022

Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs’ safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in the clinical setting. The current evidence points out that TCAs are safe and beneficial to treat neuropathic pain associated with cancer and chemotherapy, and they block different molecular pathways used by cancer cells from different locations for tumor growth and promotion. Likewise, ongoing clinical trials evaluating the antineoplastic effects of TCAs are discussed. TCAs are very biologically active compounds, and their repurposing as antitumoral drugs is a promising and straightforward approach to treat specific cancer subtypes and to further define their molecular targets, as well as an interesting starting point to design analogues with increased antitumoral activity.