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Open AccessEditorial

Sarcomas: New Biomarkers and Therapeutic Strategies

by Tomoki Nakamura

Cancers 2021, 13(20), 5213; https://doi.org/10.3390/cancers13205213 - 18 Oct 2021

Viewed by 1321

Abstract

Bone and soft tissue sarcoma (STS) are heterogeneous diseases comprised of various molecular and histologic subtypes [...] Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

Research

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Open AccessArticle

CD11c-CD8 Spatial Cross Presentation: A Novel Approach to Link Immune Surveillance and Patient Survival in Soft Tissue Sarcoma

by Yanhong Su, Panagiotis Tsagkozis, Andri Papakonstantinou, Nicholas P. Tobin, Okan Gultekin, Anna Malmerfelt, Katrine Ingelshed, Shi Yong Neo, Johanna Lundquist, Wiem Chaabane, Maya H. Nisancioglu, Lina W. Leiss, Arne Östman, Jonas Bergh, Saikiran Sedimbi, Kaisa Lehti, Andreas Lundqvist, Christina L. Stragliotto, Felix Haglund and Monika Ehnman

Cancers 2021, 13(5), 1175; https://doi.org/10.3390/cancers13051175 - 9 Mar 2021

Cited by 1 | Viewed by 4581

Abstract

Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore [...] Read more.

Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore expected to be highly warranted. In this study, intratumoral spatial cross presentation was investigated as a novel concept where immune cell composition in the tumor microenvironment was suggested to act as a proxy for immune surveillance. Double immunohistochemistry revealed a prognostic role of direct spatial interactions between CD11c+ antigen-presenting cells (APCs) and CD8+ cells in contrast to each marker alone in a soft tissue sarcoma (STS) cohort of 177 patients from the Karolinska University Hospital (MFS p = 0.048, OS p = 0.025). The survival benefit was verified in multivariable analysis (MFS p = 0.012, OS p = 0.004). Transcriptomics performed in the TCGA sarcoma cohort confirmed the prognostic value of combining CD11c with CD8 (259 patients, p = 0.005), irrespective of FOXP3 levels and in a CD274 (PD-LI)-rich tumor microenvironment. Altogether, this study presents a histopathological approach to link immune surveillance and patient survival in STS. Notably, spatial cross presentation as a prognostic marker is distinct from therapy response-predictive biomarkers such as immune checkpoint molecules of the PD-L1/PD1 pathway. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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20 pages, 4721 KiB

Open AccessEditor’s ChoiceArticle

Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells

by Julie Lafontaine, Guillaume B. Cardin, Nicolas Malaquin, Jean-Sébastien Boisvert, Francis Rodier and Philip Wong

Cancers 2021, 13(3), 386; https://doi.org/10.3390/cancers13030386 - 21 Jan 2021

Cited by 30 | Viewed by 4642

Abstract

Radiotherapy (RT) is a key component of cancer treatment. Most of the time, radiation is given after surgery but for soft-tissue sarcomas (STS), pre-surgical radiation is commonly utilized. However, despite improvements in RT accuracy, the rate of local recurrence remains high and is [...] Read more.

Radiotherapy (RT) is a key component of cancer treatment. Most of the time, radiation is given after surgery but for soft-tissue sarcomas (STS), pre-surgical radiation is commonly utilized. However, despite improvements in RT accuracy, the rate of local recurrence remains high and is the major cause of death for patients with STS. A better understanding of cell fates in response to RT could provide new therapeutic options to enhance tumour cell killing by RT and facilitate surgical resection. Here, we showed that irradiated STS cell cultures do not die but instead undergo therapy-induced senescence (TIS), which is characterized by proliferation arrest, senescence-associated β-galactosidase activity, secretion of inflammatory cytokines and persistent DNA damage. STS-TIS was also associated with increased levels of the anti-apoptotic Bcl-2 family of proteins which rendered cells targetable using senolytic Bcl-2 inhibitors. As oppose to radiation alone, the addition of senolytic agents Venetoclax (ABT-199) or Navitoclax (ABT-263) after irradiation induced a rapid apoptotic cell death in STS monolayer cultures and in a more complex three-dimensional culture model. Together, these data suggest a new promising therapeutic approach for sarcoma patients who receive neoadjuvant RT. The addition of senolytic agents to radiation treatments may significantly reduce tumour volume prior to surgery and thereby improve the clinical outcome of patients. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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17 pages, 1084 KiB

Open AccessArticle

The Role of Plastic Reconstructive Surgery in Surgical Therapy of Soft Tissue Sarcomas

by Rebekka Götzl, Sebastian Sterzinger, Andreas Arkudas, Anja M. Boos, Sabine Semrau, Nikolaos Vassos, Robert Grützmann, Abbas Agaimy, Werner Hohenberger, Raymund E. Horch and Justus P. Beier

Cancers 2020, 12(12), 3534; https://doi.org/10.3390/cancers12123534 - 26 Nov 2020

Cited by 13 | Viewed by 2358

Abstract

Background: Soft tissue sarcoma (STS) treatment is an interdisciplinary challenge. Along with radio(chemo)therapy, surgery plays the central role in STS treatment. Little is known about the impact of reconstructive surgery on STS, particularly whether reconstructive surgery enhances STS resection success with the usage [...] Read more.

Background: Soft tissue sarcoma (STS) treatment is an interdisciplinary challenge. Along with radio(chemo)therapy, surgery plays the central role in STS treatment. Little is known about the impact of reconstructive surgery on STS, particularly whether reconstructive surgery enhances STS resection success with the usage of flaps. Here, we analyzed the 10-year experience at a university hospital’s Comprehensive Cancer Center, focusing on the role of reconstructive surgery. Methods: We performed a retrospective analysis of STS-patients over 10 years. We investigated patient demographics, diagnosis, surgical management, tissue/function reconstruction, complication rates, resection status, local recurrence and survival. Results: Analysis of 290 patients showed an association between clear surgical margin (R0) resections and higher-grade sarcoma in patients with free flaps. Major complications were lower with primary wound closure than with flaps. Comparison of reconstruction techniques showed no significant differences in complication rates. Wound healing was impaired in STS recurrence. The local recurrence risk was over two times higher with primary wound closure than with flaps. Conclusion: Defect reconstructions in STS are reliable and safe. Plastic surgeons should have a permanent place in interdisciplinary surgical STS treatment, with the full armamentarium of reconstruction methods. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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14 pages, 1672 KiB

Open AccessArticle

Sonic Hedgehog Signature in Pediatric Primary Bone Tumors: Effects of the GLI Antagonist GANT61 on Ewing’s Sarcoma Tumor Growth

by Mathilde Mullard, Marie Cadé, Sarah Morice, Maryne Dupuy, Geoffroy Danieau, Jérome Amiaud, Sarah Renault, Frédéric Lézot, Régis Brion, Rose Anne Thepault, Benjamin Ory, François Lamoureux, Isabelle Corre, Bénédicte Brounais-LeRoyer, Françoise Rédini and Franck Verrecchia

Cancers 2020, 12(11), 3438; https://doi.org/10.3390/cancers12113438 - 19 Nov 2020

Cited by 10 | Viewed by 2295

Abstract

Osteosarcoma (OS) and Ewing’s sarcoma (ES) are the most common malignant bone tumors in children and adolescents. In many cases, the prognosis remains very poor. The Sonic hedgehog (SHH) signaling pathway, strongly involved in the development of many cancers, regulate transcription via the [...] Read more.

Osteosarcoma (OS) and Ewing’s sarcoma (ES) are the most common malignant bone tumors in children and adolescents. In many cases, the prognosis remains very poor. The Sonic hedgehog (SHH) signaling pathway, strongly involved in the development of many cancers, regulate transcription via the transcriptional factors Gli1-3. In this context, RNAseq analysis of OS and ES cell lines reveals an increase of some major compounds of the SHH signaling cascade in ES cells, such as the transcriptional factor Gli1. This increase leads to an augmentation of the transcriptional response of Gli1 in ES cell lines, demonstrating a dysregulation of Gli1 signaling in ES cells and thus the rationale for targeting Gli1 in ES. The use of a preclinical model of ES demonstrates that GANT61, an inhibitor of the transcriptional factor Gli1, reduces ES primary tumor growth. In vitro experiments show that GANT61 decreases the viability of ES cell, mainly through its ability to induce caspase-3/7-dependent cell apoptosis. Taken together, these results demonstrates that GANT61 may be a promising therapeutic strategy for inhibiting the progression of primary ES tumors. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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23 pages, 4575 KiB

Open AccessArticle

Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas

by Daniel L. Pouliquen, Alice Boissard, Cécile Henry, Stéphanie Blandin, Pascal Richomme, Olivier Coqueret and Catherine Guette

Cancers 2020, 12(11), 3384; https://doi.org/10.3390/cancers12113384 - 16 Nov 2020

Cited by 7 | Viewed by 2444

Abstract

Investigations of liver metastatic colonization suggest that the microenvironment is preordained to be intrinsically hospitable to the invasive cancer cells. To identify molecular determinants of that organotropism and potential therapeutic targets, we conducted proteomic analyses of the liver in an aggressive model of [...] Read more.

Investigations of liver metastatic colonization suggest that the microenvironment is preordained to be intrinsically hospitable to the invasive cancer cells. To identify molecular determinants of that organotropism and potential therapeutic targets, we conducted proteomic analyses of the liver in an aggressive model of sarcomatoid peritoneal mesothelioma (M5-T1). The quantitative changes between SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra) proteotype patterns of the liver from normal rats (G1), adjacent non-tumorous liver from untreated tumor-bearing rats (G2), and liver from curcumin-treated rats without hepatic metastases (G3) were compared. The results identified 12 biomarkers of raised immune response against M5-T1 cells in G3 and 179 liver biomarker changes in (G2 vs. G1) and (G3 vs. G2) but not in (G3 vs. G1). Cross-comparing these 179 candidates with proteins showing abundance changes related to increasing invasiveness in four different rat mesothelioma tumor models identified seven biomarkers specific to the M5-T1 tumor. Finally, analysis of correlations between these seven biomarkers, purine nucleoside phosphorylase being the main biomarker of immune response, and the 179 previously identified proteins revealed a network orchestrating liver colonization and treatment efficacy. These results highlight the links between potential targets, raising interesting prospects for optimizing therapies against highly invasive cancer cells exhibiting a sarcomatoid phenotype and sarcoma cells. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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21 pages, 3123 KiB

Open AccessArticle

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting

by Bérengère Dadone-Montaudié, Audrey Laroche-Clary, Aline Mongis, Emmanuel Chamorey, Ilaria Di Mauro, Vanessa Chaire, Pascal Finetti, Renaud Schiappa, François Le Loarer, Isabelle Birtwisle-Peyrottes, Jean-François Michiels, François Bertucci, Florence Pedeutour, Antoine Italiano and Laurence Bianchini

Cancers 2020, 12(10), 3058; https://doi.org/10.3390/cancers12103058 - 20 Oct 2020

Cited by 14 | Viewed by 3339

Abstract

We aimed to evaluate the therapeutic potential of the pan-FGFR inhibitor erdafitinib to treat dedifferentiated liposarcoma (DDLPS). FGFR expression and their prognostic value were assessed in a series of 694 samples of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). The effect of erdafitinib—alone or in combination with [...] Read more.

We aimed to evaluate the therapeutic potential of the pan-FGFR inhibitor erdafitinib to treat dedifferentiated liposarcoma (DDLPS). FGFR expression and their prognostic value were assessed in a series of 694 samples of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). The effect of erdafitinib—alone or in combination with other antagonists—on tumorigenicity was evaluated in vitro and in vivo. We detected overexpression of FGFR1 and/or FGFR4 in a subset of WDLPS and DDLPS and demonstrated correlation of this expression with poor prognosis. Erdafitinib treatment reduced cell viability, inducing apoptosis and strong inhibition of the ERK1/2 pathway. Combining erdafitinib with the MDM2 antagonist RG7388 exerted a synergistic effect on viability, apoptosis, and clonogenicity in one WDLPS and two DDLPS cell lines. Efficacy of this combination was confirmed in vivo on a DDLPS xenograft. Importantly, we report the efficacy of erdafitinib in one patient with refractory DDLPS showing disease stabilization for 12 weeks. We provide evidence that the FGFR pathway has therapeutic potential for a subset of DDLPS and that an FGFR1/FGFR4 expression might constitute a powerful biomarker to select patients for FGFR inhibitor clinical trials. In addition, we show that combining erdafitinib with RG7388 is a promising strategy for patients with DDLPS that deserves further investigation in the clinical setting. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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31 pages, 5554 KiB

Open AccessArticle

Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma

by Pankita H. Pandya, Lijun Cheng, M. Reza Saadatzadeh, Khadijeh Bijangi-Vishehsaraei, Shan Tang, Anthony L. Sinn, Melissa A. Trowbridge, Kathryn L. Coy, Barbara J. Bailey, Courtney N. Young, Jixin Ding, Erika A. Dobrota, Savannah Dyer, Adily Elmi, Quinton Thompson, Farinaz Barghi, Jeremiah Shultz, Eric A. Albright, Harlan E. Shannon, Mary E. Murray, Mark S. Marshall, Michael J. Ferguson, Todd E. Bertrand, L. Daniel Wurtz, Sandeep Batra, Lang Li, Jamie L. Renbarger and Karen E. Pollok Show full author list Hide full author list

Cancers 2020, 12(9), 2426; https://doi.org/10.3390/cancers12092426 - 26 Aug 2020

Cited by 10 | Viewed by 7990

Abstract

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, [...] Read more.

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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15 pages, 1859 KiB

Open AccessArticle

Integration of Serum Metabolomics into Clinical Assessment to Improve Outcome Prediction of Metastatic Soft Tissue Sarcoma Patients Treated with Trabectedin

by Gianmaria Miolo, Emanuela Di Gregorio, Asia Saorin, Davide Lombardi, Simona Scalone, Angela Buonadonna, Agostino Steffan and Giuseppe Corona

Cancers 2020, 12(7), 1983; https://doi.org/10.3390/cancers12071983 - 21 Jul 2020

Cited by 14 | Viewed by 3134

Abstract

Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers with few diagnostic or prognostic biomarkers. This metabolomics study aimed to identify new serum prognostic biomarkers to improve the prediction of overall survival in patients with metastatic STS. The study enrolled [...] Read more.

Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers with few diagnostic or prognostic biomarkers. This metabolomics study aimed to identify new serum prognostic biomarkers to improve the prediction of overall survival in patients with metastatic STS. The study enrolled 24 patients treated with the same trabectedin regimen. The baseline serum metabolomics profile, targeted to 68 metabolites encompassing amino acids and bile acids pathways, was quantified by liquid chromatography-tandem mass spectrometry. Correlations between individual metabolomics profiles and overall survival were examined and a risk model to predict survival was built by Cox multivariate regression. The median overall survival of the studied patients was 13.0 months (95% CI, 5.6–23.5). Among all the metabolites investigated, only citrulline and histidine correlated significantly with overall survival. The best Cox risk prediction model obtained integrating metabolomics and clinical data, included citrulline, hemoglobin and patients’ performance status score. It allowed to distinguish patients into a high-risk group with a low median overall survival of 2.1 months and a low- to moderate-risk group with a median overall survival of 19.1 months (p < 0.0001). The results of this metabolomics translation study indicate that citrulline, an amino acid belonging to the arginine metabolism, represents an important metabolic signature that may contribute to explain the high inter-patients overall survival variability of STS patients. The risk prediction model based on baseline serum citrulline, hemoglobin and performance status may represent a new prognostic tool for the early classification of patients with metastatic STS, according to their overall survival expectancy. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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11 pages, 429 KiB

Open AccessArticle

Prediction of Soft Tissue Sarcoma from Clinical Characteristics and Laboratory Data

by Taketsugu Fujibuchi, Joji Miyawaki, Teruki Kidani, Hiroshi Imai and Hiromasa Miura

Cancers 2020, 12(3), 679; https://doi.org/10.3390/cancers12030679 - 13 Mar 2020

Cited by 7 | Viewed by 3047

Abstract

The accurate diagnosis of soft tissue tumors may be difficult. Simple clinical characteristics or laboratory data that can predict tumor malignancy can be useful tools for diagnosing soft tissue tumors. Between 2003 and 2018, 588 patients with primary soft tissue tumors were retrospectively [...] Read more.

The accurate diagnosis of soft tissue tumors may be difficult. Simple clinical characteristics or laboratory data that can predict tumor malignancy can be useful tools for diagnosing soft tissue tumors. Between 2003 and 2018, 588 patients with primary soft tissue tumors were retrospectively reviewed. Their clinical characteristics and laboratory data were evaluated to determine their association with the diagnosis of benign, intermediate, or malignant tumor. Multivariable analysis revealed that tumor size ≥ 5.6 cm (odds ratio (OR), 6.15; p < 0.001), white blood cell (WBC) count ≥ 5700/µL (OR, 2.49; p = 0.002), hemoglobin (Hb) count ≤ 12.4 g/dL (OR, 2.56; p = 0.004), C-reactive protein (CRP) level ≥ 0.17 mg/dL (OR, 2.64; p < 0.001), and lactate dehydrogenase (LDH) level ≥ 240 IU/L (OR, 4.94; p < 0.001) were significant predictive factors for sarcoma. The sensitivity and specificity in the presence of three or more predictive factors for detecting malignant tumors were 0.58 and 0.90 respectively, and it was an appropriate threshold with the maximum Youden’s index of 0.49. Simple clinical and laboratory data were useful tools for predicting whether the tumor is malignant. Patients with soft tissue tumors that meet any three or more predictive factors should be referred to a specialist. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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10 pages, 1229 KiB

Open AccessArticle

Expression of Interleukin-6 and the Interleukin-6 Receptor Predicts the Clinical Outcomes of Patients with Soft Tissue Sarcomas

by Koichi Nakamura, Tomoki Nakamura, Takahiro Iino, Tomohito Hagi, Kouji Kita, Kunihiro Asanuma and Akihiro Sudo

Cancers 2020, 12(3), 585; https://doi.org/10.3390/cancers12030585 - 3 Mar 2020

Cited by 16 | Viewed by 2881

Abstract

Interleukin-6 (IL-6) affects the key parameters of oncogenesis, which increases the cell resistance to apoptosis, the proliferation of cancer cells, angiogenesis, invasion, malignancy, and the ability of tumor cells to respond to anticancer therapy. This study aimed to elucidate the association between IL-6 [...] Read more.

Interleukin-6 (IL-6) affects the key parameters of oncogenesis, which increases the cell resistance to apoptosis, the proliferation of cancer cells, angiogenesis, invasion, malignancy, and the ability of tumor cells to respond to anticancer therapy. This study aimed to elucidate the association between IL-6 and IL-6 receptor (IL-6R) expression in tissues and clinical outcomes in patients with soft tissue sarcomas (STSs) because, to our knowledge, this has not been done before. We enrolled 86 patients with histologically-proven localized STSs who underwent surgical resection. The cohort included 48 men and 38 women, with a mean age of 65.6 years. The mean follow-up duration was 40.5 months. The expression of IL-6 and IL-6R was immunohistochemically determined. We analyzed prognostic factors for overall survival (OS) and metastasis-free survival (MFS). High IL-6 expression was observed in 23.3% (20/86), high IL-6R expression in 44.2% (38/86), and high expression of both in 16.3% (14/86) of patients. Multivariate analysis showed that a high expression of both IL-6 and IL-6R was a prognostic factor for OS and MFS. We found that this high expression indicated that the patient had a poor prognosis for OS and MFS. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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Review

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17 pages, 592 KiB

Open AccessReview

Role of Tumor-Associated Macrophages in Sarcomas

by Tomohiro Fujiwara, John Healey, Koichi Ogura, Aki Yoshida, Hiroya Kondo, Toshiaki Hata, Miho Kure, Hiroshi Tazawa, Eiji Nakata, Toshiyuki Kunisada, Toshiyoshi Fujiwara and Toshifumi Ozaki

Cancers 2021, 13(5), 1086; https://doi.org/10.3390/cancers13051086 - 3 Mar 2021

Cited by 32 | Viewed by 4705

Abstract

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor [...] Read more.

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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13 pages, 1232 KiB

Open AccessReview

Recent Advances in Desmoid Tumor Therapy

by Andrea Napolitano, Alessandro Mazzocca, Mariella Spalato Ceruso, Alessandro Minelli, Francesca Baldo, Giuseppe Badalamenti, Marianna Silletta, Daniele Santini, Giuseppe Tonini, Lorena Incorvaia and Bruno Vincenzi

Cancers 2020, 12(8), 2135; https://doi.org/10.3390/cancers12082135 - 1 Aug 2020

Cited by 25 | Viewed by 8491

Abstract

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded [...] Read more.

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents. Full article

(This article belongs to the Special Issue Sarcomas: New Biomarkers and Therapeutic Strategies)

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