Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial
BackgroundTumor invasion and metastasis are responsible for the majority of cancer-related deaths. The identification of molecules involved in these processes is crucial to design effective treatments that can halt the progression of cancer. To spread and metastasize, tumor cells must restructure th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1238464/full |
| _version_ | 1797201561488719872 |
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| author | Antonio Asensi-Cantó Antonio Asensi-Cantó Antonio Asensi-Cantó Edith Rodríguez-Braun Asunción Beltrán-Videla Ana María Hurtado Ana María Hurtado Pablo Conesa-Zamora Pablo Conesa-Zamora |
| author_facet | Antonio Asensi-Cantó Antonio Asensi-Cantó Antonio Asensi-Cantó Edith Rodríguez-Braun Asunción Beltrán-Videla Ana María Hurtado Ana María Hurtado Pablo Conesa-Zamora Pablo Conesa-Zamora |
| author_sort | Antonio Asensi-Cantó |
| collection | DOAJ |
| description | BackgroundTumor invasion and metastasis are responsible for the majority of cancer-related deaths. The identification of molecules involved in these processes is crucial to design effective treatments that can halt the progression of cancer. To spread and metastasize, tumor cells must restructure their cytoskeleton and emit protrusions. A key molecule in this process of creating these invading structures is Fascin1, the main protein involved in the formation of actin cytoskeleton bundles and a consistent marker of bad prognosis in several types of cancer. Recent studies have shown that imipramine, an FDA- and EMA-approved antidepressant, can block Fascin1and prevent the formation of actin bundles, making it a promising candidate for the treatment of Fascin1-expressing cancers. As a result, a clinical trial will be conducted to assess the efficacy of imipramine being the first experimental clinical study selecting patients based on Fascin1 expression.MethodsThe HITCLIF trial is a multicenter, double-blind, placebo-controlled, randomized and non-commercial phase II clinical trial conducted in parallel groups to evaluate the effectiveness of the tricyclic antidepressant imipramine as anti-invasive agent in the treatment of localized colon, rectal and triple negative breast cancer patients with overexpression of Fascin1. Eligible patients will be randomly assigned, in a 1:1 ratio, to receive imipramine or placebo. Patients will be stratified into 2 groups according to whether administration of imipramine is concomitant with neoadjuvant chemotherapy regimen. Group A will receive imipramine alone without neoadjuvant chemotherapy, while Group B will receive imipramine treatment along with the standard neoadjuvant chemotherapy regimen. The primary endpoint of the trial is the grade of alteration in the prognostic histopathological features at invasive margins (tumor budding, cytoplasmic pseudo-fragments, tumor growth pattern, and peritumoral lymphocytic infiltration).DiscussionFascin1 is an interesting therapeutical target as it plays a causative role in the invasion and metastasis of cancer cells. Moreover, its expression is virtually absent in normal epithelia but highly expressed in cancer with bad prognosis. In silico, in vitro and in vivo studies by our group have demonstrated that the antidepressant imipramine has Fascin1-dependant anti-invasive and anti-metastatic effects in colorectal cancer cells. Now we are recruiting patients in a clinical trial based on Fascin1 over-expression in which administration of imipramine will be carried out during the period between the diagnosis biopsy and surgical resection to explore the drug effects on tumor invasive front.Clinical trial registrationhttps:///www.clinicaltrialsregister.eu/ctr-search/trial/2021-001328-17/ES, identifier 2021-001328-17. |
| first_indexed | 2024-03-11T21:04:06Z |
| format | Article |
| id | doaj.art-e2e9a84e5e264fed9ebd481f1e51f5b5 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-24T07:49:30Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e2e9a84e5e264fed9ebd481f1e51f5b52024-04-18T14:08:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-09-011310.3389/fonc.2023.12384641238464Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trialAntonio Asensi-Cantó0Antonio Asensi-Cantó1Antonio Asensi-Cantó2Edith Rodríguez-Braun3Asunción Beltrán-Videla4Ana María Hurtado5Ana María Hurtado6Pablo Conesa-Zamora7Pablo Conesa-Zamora8Facultad de Ciencias de la Salud, Universidad Católica de Murcia (UCAM), Guadalupe, SpainPharmacy Department, Hospital Universitario Santa Lucía, Cartagena, SpainMolecular Pathology and Pharmacogenetics Research Group, Instituto Murciano de Investigación Biosanitaria (IMIB), Hospital Universitario Santa Lucía, Cartagena, SpainOncology Department, Hospital Universitario Santa Lucía, Cartagena, SpainMolecular Pathology and Pharmacogenetics Research Group, Instituto Murciano de Investigación Biosanitaria (IMIB), Hospital Universitario Santa Lucía, Cartagena, SpainMolecular Pathology and Pharmacogenetics Research Group, Instituto Murciano de Investigación Biosanitaria (IMIB), Hospital Universitario Santa Lucía, Cartagena, SpainInnmunobiology for Aquaculture Research Group, Cellular Biology and Histology Department, Universidad de Murcia, Murcia, SpainMolecular Pathology and Pharmacogenetics Research Group, Instituto Murciano de Investigación Biosanitaria (IMIB), Hospital Universitario Santa Lucía, Cartagena, SpainLaboratory Medicine Department, Hospital Universitario Santa Lucía, Cartagena, SpainBackgroundTumor invasion and metastasis are responsible for the majority of cancer-related deaths. The identification of molecules involved in these processes is crucial to design effective treatments that can halt the progression of cancer. To spread and metastasize, tumor cells must restructure their cytoskeleton and emit protrusions. A key molecule in this process of creating these invading structures is Fascin1, the main protein involved in the formation of actin cytoskeleton bundles and a consistent marker of bad prognosis in several types of cancer. Recent studies have shown that imipramine, an FDA- and EMA-approved antidepressant, can block Fascin1and prevent the formation of actin bundles, making it a promising candidate for the treatment of Fascin1-expressing cancers. As a result, a clinical trial will be conducted to assess the efficacy of imipramine being the first experimental clinical study selecting patients based on Fascin1 expression.MethodsThe HITCLIF trial is a multicenter, double-blind, placebo-controlled, randomized and non-commercial phase II clinical trial conducted in parallel groups to evaluate the effectiveness of the tricyclic antidepressant imipramine as anti-invasive agent in the treatment of localized colon, rectal and triple negative breast cancer patients with overexpression of Fascin1. Eligible patients will be randomly assigned, in a 1:1 ratio, to receive imipramine or placebo. Patients will be stratified into 2 groups according to whether administration of imipramine is concomitant with neoadjuvant chemotherapy regimen. Group A will receive imipramine alone without neoadjuvant chemotherapy, while Group B will receive imipramine treatment along with the standard neoadjuvant chemotherapy regimen. The primary endpoint of the trial is the grade of alteration in the prognostic histopathological features at invasive margins (tumor budding, cytoplasmic pseudo-fragments, tumor growth pattern, and peritumoral lymphocytic infiltration).DiscussionFascin1 is an interesting therapeutical target as it plays a causative role in the invasion and metastasis of cancer cells. Moreover, its expression is virtually absent in normal epithelia but highly expressed in cancer with bad prognosis. In silico, in vitro and in vivo studies by our group have demonstrated that the antidepressant imipramine has Fascin1-dependant anti-invasive and anti-metastatic effects in colorectal cancer cells. Now we are recruiting patients in a clinical trial based on Fascin1 over-expression in which administration of imipramine will be carried out during the period between the diagnosis biopsy and surgical resection to explore the drug effects on tumor invasive front.Clinical trial registrationhttps:///www.clinicaltrialsregister.eu/ctr-search/trial/2021-001328-17/ES, identifier 2021-001328-17.https://www.frontiersin.org/articles/10.3389/fonc.2023.1238464/fullcancermetastasiscolorectal cancerbreast cancerimipramineFascin1 |
| spellingShingle | Antonio Asensi-Cantó Antonio Asensi-Cantó Antonio Asensi-Cantó Edith Rodríguez-Braun Asunción Beltrán-Videla Ana María Hurtado Ana María Hurtado Pablo Conesa-Zamora Pablo Conesa-Zamora Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial Frontiers in Oncology cancer metastasis colorectal cancer breast cancer imipramine Fascin1 |
| title | Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial |
| title_full | Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial |
| title_fullStr | Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial |
| title_full_unstemmed | Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial |
| title_short | Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial |
| title_sort | effects of imipramine on cancer patients over expressing fascin1 description of the hitclif clinical trial |
| topic | cancer metastasis colorectal cancer breast cancer imipramine Fascin1 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1238464/full |
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