Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan
Mariane S Fontes,1,2 Daniel Vargas Pivato de Almeida,2,3 Clarissa Cavalin,1 Scott T Tagawa4 1Oncology Department, Oncoclinicas Group, Rio de Janeiro, Brazil; 2LACOG, Latin American Cooperative Oncology Group, Brazil; 3Oncology Department, Oncoclinicas Group, Porto Alegre, Brazil; 4Weill Cornell Medi...
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Language: | English |
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Dove Medical Press
2022-12-01
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Series: | OncoTargets and Therapy |
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Online Access: | https://www.dovepress.com/targeted-therapy-for-locally-advanced-or-metastatic-urothelial-cancer--peer-reviewed-fulltext-article-OTT |
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author | Fontes MS Vargas Pivato de Almeida D Cavalin C Tagawa ST |
author_facet | Fontes MS Vargas Pivato de Almeida D Cavalin C Tagawa ST |
author_sort | Fontes MS |
collection | DOAJ |
description | Mariane S Fontes,1,2 Daniel Vargas Pivato de Almeida,2,3 Clarissa Cavalin,1 Scott T Tagawa4 1Oncology Department, Oncoclinicas Group, Rio de Janeiro, Brazil; 2LACOG, Latin American Cooperative Oncology Group, Brazil; 3Oncology Department, Oncoclinicas Group, Porto Alegre, Brazil; 4Weill Cornell Medicine, New York, NY, USACorrespondence: Scott T Tagawa, Email stt2007@med.cornell.eduAbstract: Urothelial carcinoma is the second most frequent genitourinary malignancy. Despite the poor prognosis, new treatment options have emerged and have expanded the therapeutic landscape for the disease. Although major improvements have been achieved, many patients experience rapid disease progression and low responses in subsequent lines of therapy. Sacituzumab govitecan is an ADC that targets Trop-2, which is highly expressed in urothelial cancers. Promising results in early clinical trials have led to further drug development which confirmed encouraging efficacy. Sacituzumab govitecan has been given accelerated approval in 2021 for patients with locally advanced and metastatic urothelial cancer who previously received a platinum containing chemotherapy and either a programmed death receptor-1 or programmed death ligand inhibitor. The results are promising, with encouraging efficacy and safety, however responses are not universal. There is a growing comprehension of mechanisms of resistance and predictive biomarkers that are crucial to improving outcomes. In this review, we summarize the current knowledge on antibody–drug conjugates and the clinical findings that led to the approval of Sacituzumab govitecan and discuss the therapeutic potential of new combinations, mechanisms of resistance and predictive biomarkers.Keywords: antibody–drug conjugate, ADC, bladder cancer, Trop-2, human trophoblast cell surface antigen 2, SN-38 |
first_indexed | 2024-04-11T05:31:36Z |
format | Article |
id | doaj.art-87f28f8128ea47e1af4f306598f26f0c |
institution | Directory Open Access Journal |
issn | 1178-6930 |
language | English |
last_indexed | 2024-04-11T05:31:36Z |
publishDate | 2022-12-01 |
publisher | Dove Medical Press |
record_format | Article |
series | OncoTargets and Therapy |
spelling | doaj.art-87f28f8128ea47e1af4f306598f26f0c2022-12-22T18:12:17ZengDove Medical PressOncoTargets and Therapy1178-69302022-12-01Volume 151531154280524Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab GovitecanFontes MSVargas Pivato de Almeida DCavalin CTagawa STMariane S Fontes,1,2 Daniel Vargas Pivato de Almeida,2,3 Clarissa Cavalin,1 Scott T Tagawa4 1Oncology Department, Oncoclinicas Group, Rio de Janeiro, Brazil; 2LACOG, Latin American Cooperative Oncology Group, Brazil; 3Oncology Department, Oncoclinicas Group, Porto Alegre, Brazil; 4Weill Cornell Medicine, New York, NY, USACorrespondence: Scott T Tagawa, Email stt2007@med.cornell.eduAbstract: Urothelial carcinoma is the second most frequent genitourinary malignancy. Despite the poor prognosis, new treatment options have emerged and have expanded the therapeutic landscape for the disease. Although major improvements have been achieved, many patients experience rapid disease progression and low responses in subsequent lines of therapy. Sacituzumab govitecan is an ADC that targets Trop-2, which is highly expressed in urothelial cancers. Promising results in early clinical trials have led to further drug development which confirmed encouraging efficacy. Sacituzumab govitecan has been given accelerated approval in 2021 for patients with locally advanced and metastatic urothelial cancer who previously received a platinum containing chemotherapy and either a programmed death receptor-1 or programmed death ligand inhibitor. The results are promising, with encouraging efficacy and safety, however responses are not universal. There is a growing comprehension of mechanisms of resistance and predictive biomarkers that are crucial to improving outcomes. In this review, we summarize the current knowledge on antibody–drug conjugates and the clinical findings that led to the approval of Sacituzumab govitecan and discuss the therapeutic potential of new combinations, mechanisms of resistance and predictive biomarkers.Keywords: antibody–drug conjugate, ADC, bladder cancer, Trop-2, human trophoblast cell surface antigen 2, SN-38https://www.dovepress.com/targeted-therapy-for-locally-advanced-or-metastatic-urothelial-cancer--peer-reviewed-fulltext-article-OTTantibody drug conjugateadcbladder cancertrop-2human trophoblast cell surface antigen 2sn-38 |
spellingShingle | Fontes MS Vargas Pivato de Almeida D Cavalin C Tagawa ST Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan OncoTargets and Therapy antibody drug conjugate adc bladder cancer trop-2 human trophoblast cell surface antigen 2 sn-38 |
title | Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan |
title_full | Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan |
title_fullStr | Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan |
title_full_unstemmed | Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan |
title_short | Targeted Therapy for Locally Advanced or Metastatic Urothelial Cancer (mUC): Therapeutic Potential of Sacituzumab Govitecan |
title_sort | targeted therapy for locally advanced or metastatic urothelial cancer muc therapeutic potential of sacituzumab govitecan |
topic | antibody drug conjugate adc bladder cancer trop-2 human trophoblast cell surface antigen 2 sn-38 |
url | https://www.dovepress.com/targeted-therapy-for-locally-advanced-or-metastatic-urothelial-cancer--peer-reviewed-fulltext-article-OTT |
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