Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level
Abstract
:Simple Summary
Abstract
1. Introduction
2. Molecular Markers Associated with Prognosis
2.1. Microenvironment
2.1.1. Markers of Infiltration
B Cells
T Cells
Macrophages
2.1.2. Immune Checkpoints
PD1-PDL1
Others (IDO, LAG3, TIM3)
2.2. Genetics
2.2.1. Tumor Mutation Burden
2.2.2. Microsatellite Instability
2.2.3. Molecular Biomarkers
Tumor Suppressor Genes
Oncogenes
MicroRNA
Long Non-Coding RNA
Telomere-Maintenance Mechanism
3. Metabolite Biomarkers
4. Circulating Biomarkers
5. Biomarkers in Clinical Trials
6. Limitations
7. Future Perspectives and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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A. Main Molecular Markers Associated with Prognosis in STSs | ||
Molecular Marker | Prognosis | References |
Microenvironment | ||
high B cells | better survival | [24] |
high CD8+ T cells | improvement in survival | [24,29,30,31,32] |
low CD8+ T cells at relapse | poor survival | [18] |
high CD4+ T cells | improvement in survival | [24,28] |
low CD163+ TIMs | favorable survival | [15] |
high levels CD163+ | improvement in survival | [22] |
PDL1+ | worse prognosis | [39] |
LAG3+ CD8+ T cells | severe prognosis | [45] |
LAG3+ CD4+ T cells | severe prognosis | [45] |
Genetics | ||
miR26a-2c amplification | poor survival | [95] |
high expression of miR-17-92 cluster | poor prognosis | [101] |
miRNA panel * | predicted in metastatic events | [108] |
miR-138 overexpression | negative correlation with MFS | [116] |
miR-210 | severe prognosis | [121] |
LncRNAs: LINC00680, AC006129.2, RP11-274B21.9 and RP11-713P17.3 | favorable prognosis | [124] |
LncRNAs: RP11-560J1.2, AP001432.14, RP4-665J23.1, RP11-230G5.2, BACH1-IT2, and RP11504A18.1 | severe prognosis | [124] |
citrulline shortage | poor outcome | [137] |
B. Main Molecular Markers Associated with Sensitivity/Resistance to Therapy in STSs. | ||
Molecular Marker | Sensitivity/Resistance to Therapy | References |
CD8+ and CD4+ T cells | response to therapies | [24] |
Alterations in CD68+, CD163+ | neoadjuvant chemotherapy | [34] |
increase in PDL1 levels | radiotherapy | [40] |
IDO1/KP signaling pathway | resistance to PD1 inhibitors | [42] |
miR-485-3p–Top2α–NF-YB pathway | sensitivity to therapies | [101,102] |
Immune Checkpoint Inhibitor | Trial Number | Phase | Status |
---|---|---|---|
Ipilimumab (anti-CTLA4) | NCT01445379 | I | Completed |
Pembrolizumab (anti-PD1) | NCT02301039NCT03316573 | II II | Completed Recruiting |
Toripalimab (anti-PD1) | NCT03474640 | I | Recruiting |
Spartalizumab (anti-PD1) | NCT04802876 | II | Not yet recruiting |
Immune Checkpoint Inhibitors | Other Agents | Trial Number | Phase | Status |
---|---|---|---|---|
Immune checkpoint inhibitors in combination with other immunotherapy agents | ||||
Pembrolizumab | IDO 1 Inhibitor (i) (epacadostat) | NCT03414229 | II | Active, not recruiting |
Nivolumab (anti-PD1) | Ipilimumab (anti-CTLA4) | NCT04741438 | III | Recruiting |
Relatlimab (anti-LAG3) | NCT04095208 | II | Recruiting | |
NKTR-214 | NCT03282344 | II | Active, not recruiting | |
Immune checkpoint inhibitors in combination with chemotherapy or radiation therapy | ||||
Atezolizumab (anti-PDL1) | Radiation therapy | NCT03474094 | II | Recruiting |
Nivolumab | Paclitaxel | NCT04339738 | II | Recruiting |
Trabectedin | NCT03590210 | II | Active, not recruiting | |
T-VEC and Trabectedin | NCT03886311 | II | Recruiting | |
Pembrolizumab | Radiation therapy | NCT03338959 | I-II | Recruiting |
Eribuline | NCT03899805 | II | Active, not recruiting | |
T-VEC | NCT03069378 | II | Recruiting | |
Lenvatinib (VEGFR/FGFR-i) | NCT04784247 | II | Recruiting | |
Axitinib (VEGFR- i) | NCT02636725 | II | Active, not recruiting | |
Immune checkpoint inhibitors in combination with other agents | ||||
Atezolizumab | Bevacizumab (VEGF-i) | NCT03141684 | II | Recruiting |
Rucaparib (PARP-i) | NCT04216953 | I-II | Recruiting | |
Cobimetinib (MEK-i) | NCT04624178 | II | Recruiting | |
Dual immune checkpoint inhibitors therapy in combination with other agents | ||||
Nivolumab plus ipilimumab | Cabozantinib (VEGFR/MET/AXL-i) | NCT04551430 | II | Recruiting |
Trabectedin | NCT03138161 | I-II | Recruiting |
PARP-Inhibitor | Other Agents | NCT Trial Number | Phase | Status |
---|---|---|---|---|
Olaparib | Radiation therapy | NCT02787642 | I | Recruiting |
Olaparib | Temozolomide | NCT01858168 | I | Recruiting |
Olaparib | Durvalumab | NCT03784014 | III | Recruiting |
Olaparib | Trabectedin | NCT04076579 | II | Recruiting |
Olaparib | Pembrolizumab | NCT04123366 | II | Recruiting |
Olaparib | - | NCT03233204 | II | Recruiting |
Rucaparib | - | NCT04171700 | II | Recruiting |
Multitargeted TKI-i | Other Agents | NCT Trial Number | Phase | Status |
---|---|---|---|---|
EZH2 inhibitors (tazemetostat) | Doxorubicin | NCT04204941 | III | Recruiting |
Nab-rapamycin | Nivolumab | NCT03190174 | I-II | Recruiting |
TRK inhibitor (Larotrectinib) | - | NCT02576431 | II | Recruiting |
CDK4 inhibitors (Abemaciclib) | - | NCT04040205 | II | Recruiting |
Temozolomide and Irinotecan | NCT04238819 | I | Recruiting |
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Pillozzi, S.; Bernini, A.; Palchetti, I.; Crociani, O.; Antonuzzo, L.; Campanacci, D.; Scoccianti, G. Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level. Cancers 2021, 13, 3044. https://doi.org/10.3390/cancers13123044
Pillozzi S, Bernini A, Palchetti I, Crociani O, Antonuzzo L, Campanacci D, Scoccianti G. Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level. Cancers. 2021; 13(12):3044. https://doi.org/10.3390/cancers13123044
Chicago/Turabian StylePillozzi, Serena, Andrea Bernini, Ilaria Palchetti, Olivia Crociani, Lorenzo Antonuzzo, Domenico Campanacci, and Guido Scoccianti. 2021. "Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level" Cancers 13, no. 12: 3044. https://doi.org/10.3390/cancers13123044