Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer
The dynamic interplay between pro-death and pro-survival Bcl-2 family proteins is responsible for a cell’s fate. Due to the recognized relevance of this family in cancer progression and response to therapy, different efforts have made in recent years in order to develop small molecules able to targe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1287 |
| _version_ | 1797567275697438720 |
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| author | Simona D’Aguanno Donatella Del Bufalo |
| author_facet | Simona D’Aguanno Donatella Del Bufalo |
| author_sort | Simona D’Aguanno |
| collection | DOAJ |
| description | The dynamic interplay between pro-death and pro-survival Bcl-2 family proteins is responsible for a cell’s fate. Due to the recognized relevance of this family in cancer progression and response to therapy, different efforts have made in recent years in order to develop small molecules able to target anti-apoptotic proteins such as Bcl-2, Bcl-xL and Mcl-1. The limitations of the first Bcl-2 family targeted drugs, regarding on-target and off-target toxicities, have been overcome with the development of venetoclax (ABT-199), the first BH3 mimetic inhibitor approved by the FDA. The purpose of this review is to discuss the state-of-the-art in the development of drugs targeting Bcl-2 anti-apoptotic proteins and to highlight the potential of their application as single agents or in combination for improving anti-cancer therapy, focusing in particular on solid tumors. |
| first_indexed | 2024-03-10T19:39:21Z |
| format | Article |
| id | doaj.art-1aa1f3fbb0cf4190a2345bfcb2586409 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:39:21Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1aa1f3fbb0cf4190a2345bfcb25864092023-11-20T01:19:51ZengMDPI AGCells2073-44092020-05-0195128710.3390/cells9051287Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in CancerSimona D’Aguanno0Donatella Del Bufalo1Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, ItalyPreclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, ItalyThe dynamic interplay between pro-death and pro-survival Bcl-2 family proteins is responsible for a cell’s fate. Due to the recognized relevance of this family in cancer progression and response to therapy, different efforts have made in recent years in order to develop small molecules able to target anti-apoptotic proteins such as Bcl-2, Bcl-xL and Mcl-1. The limitations of the first Bcl-2 family targeted drugs, regarding on-target and off-target toxicities, have been overcome with the development of venetoclax (ABT-199), the first BH3 mimetic inhibitor approved by the FDA. The purpose of this review is to discuss the state-of-the-art in the development of drugs targeting Bcl-2 anti-apoptotic proteins and to highlight the potential of their application as single agents or in combination for improving anti-cancer therapy, focusing in particular on solid tumors.https://www.mdpi.com/2073-4409/9/5/1287cancerBcl-2inhibitors |
| spellingShingle | Simona D’Aguanno Donatella Del Bufalo Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer Cells cancer Bcl-2 inhibitors |
| title | Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer |
| title_full | Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer |
| title_fullStr | Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer |
| title_full_unstemmed | Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer |
| title_short | Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer |
| title_sort | inhibition of anti apoptotic bcl 2 proteins in preclinical and clinical studies current overview in cancer |
| topic | cancer Bcl-2 inhibitors |
| url | https://www.mdpi.com/2073-4409/9/5/1287 |
| work_keys_str_mv | AT simonadaguanno inhibitionofantiapoptoticbcl2proteinsinpreclinicalandclinicalstudiescurrentoverviewincancer AT donatelladelbufalo inhibitionofantiapoptoticbcl2proteinsinpreclinicalandclinicalstudiescurrentoverviewincancer |