Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives
Testicular germ cell tumors share a marked sensitivity to cisplatin, contributing to their overall good prognosis. However, a subset of patients develop resistance to platinum-based treatments, by still-elusive mechanisms, experiencing poor quality of life due to multiple (often ineffective) interve...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/6/1601 |
| _version_ | 1797564996769546240 |
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| author | João Lobo Carmen Jerónimo Rui Henrique |
| author_facet | João Lobo Carmen Jerónimo Rui Henrique |
| author_sort | João Lobo |
| collection | DOAJ |
| description | Testicular germ cell tumors share a marked sensitivity to cisplatin, contributing to their overall good prognosis. However, a subset of patients develop resistance to platinum-based treatments, by still-elusive mechanisms, experiencing poor quality of life due to multiple (often ineffective) interventions and, eventually, dying from disease. Currently, there is a lack of defined treatment opportunities for these patients that tackle the mechanism(s) underlying the emergence of resistance. Herein, we aim to provide a multifaceted overview of cisplatin resistance in testicular germ cell tumors, from the clinical perspective, to the pathobiology (including mechanisms contributing to induction of the resistant phenotype), to experimental models available for studying this occurrence. We provide a systematic summary of pre-target, on-target, post-target, and off-target mechanisms putatively involved in cisplatin resistance, providing data from preclinical studies and from those attempting validation in clinical samples, including those exploring specific alterations as therapeutic targets, some of them included in ongoing clinical trials. We briefly discuss the specificities of resistance related to teratoma (differentiated) phenotype, including the phenomena of growing teratoma syndrome and development of somatic-type malignancy. Cisplatin resistance is most likely multifactorial, and a combination of therapeutic strategies will most likely produce the best clinical benefit. |
| first_indexed | 2024-03-10T19:05:45Z |
| format | Article |
| id | doaj.art-0903c2efb4e84c53a918ef19cadaf764 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:05:45Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0903c2efb4e84c53a918ef19cadaf7642023-11-20T04:07:02ZengMDPI AGCancers2072-66942020-06-01126160110.3390/cancers12061601Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various PerspectivesJoão Lobo0Carmen Jerónimo1Rui Henrique2Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalCancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalCancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalTesticular germ cell tumors share a marked sensitivity to cisplatin, contributing to their overall good prognosis. However, a subset of patients develop resistance to platinum-based treatments, by still-elusive mechanisms, experiencing poor quality of life due to multiple (often ineffective) interventions and, eventually, dying from disease. Currently, there is a lack of defined treatment opportunities for these patients that tackle the mechanism(s) underlying the emergence of resistance. Herein, we aim to provide a multifaceted overview of cisplatin resistance in testicular germ cell tumors, from the clinical perspective, to the pathobiology (including mechanisms contributing to induction of the resistant phenotype), to experimental models available for studying this occurrence. We provide a systematic summary of pre-target, on-target, post-target, and off-target mechanisms putatively involved in cisplatin resistance, providing data from preclinical studies and from those attempting validation in clinical samples, including those exploring specific alterations as therapeutic targets, some of them included in ongoing clinical trials. We briefly discuss the specificities of resistance related to teratoma (differentiated) phenotype, including the phenomena of growing teratoma syndrome and development of somatic-type malignancy. Cisplatin resistance is most likely multifactorial, and a combination of therapeutic strategies will most likely produce the best clinical benefit.https://www.mdpi.com/2072-6694/12/6/1601testicular germ-cell tumorscisplatinresistancetargeted treatment |
| spellingShingle | João Lobo Carmen Jerónimo Rui Henrique Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives Cancers testicular germ-cell tumors cisplatin resistance targeted treatment |
| title | Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives |
| title_full | Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives |
| title_fullStr | Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives |
| title_full_unstemmed | Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives |
| title_short | Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives |
| title_sort | cisplatin resistance in testicular germ cell tumors current challenges from various perspectives |
| topic | testicular germ-cell tumors cisplatin resistance targeted treatment |
| url | https://www.mdpi.com/2072-6694/12/6/1601 |
| work_keys_str_mv | AT joaolobo cisplatinresistanceintesticulargermcelltumorscurrentchallengesfromvariousperspectives AT carmenjeronimo cisplatinresistanceintesticulargermcelltumorscurrentchallengesfromvariousperspectives AT ruihenrique cisplatinresistanceintesticulargermcelltumorscurrentchallengesfromvariousperspectives |