Improving the efficacy of osteosarcoma therapy: combining drugs that turn cancer cell ‘don't eat me’ signals off and ‘eat me’ signals on

Mohanty, Suchismita; Aghighi, Maryam; Yerneni, Ketan; Theruvath, Johanna; Daldrup‐Link, Heike E.

doi:10.1002/1878-0261.12556

Cited by 32 publications

(29 citation statements)

References 50 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have recently shown that this effect can be visualized with ferumoxytol-MRI. Osteosarcomas in mouse models demonstrated significantly stronger ferumoxytol enhancement and significantly increased TAM quantities after CD47 mAb plus doxorubicin combination therapy compared to CD47 mAb (P = 0.02) and doxorubicin monotherapy (P = 0.001) 186. Since cytotoxic drugs may be either immunostimulatory or immunosuppressive 138, ferumoxytol-MRI might be useful as a new tool to find synergistic drug combinations and recognize antagonistic combinations.…”

Section: Monitoring Cancer Immunotherapy With Iron Oxide Nanoparticlesmentioning

confidence: 98%

The yin and yang of imaging tumor associated macrophages with PET and MRI

Mukherjee¹,

Sonanini²,

Maurer³

et al. 2019

Theranostics

View full text Add to dashboard Cite

Tumor associated macrophages (TAM) are key players in the cancer microenvironment. Molecular imaging modalities such as MRI and PET can be used to track and monitor TAM dynamics in tumors non-invasively, based on specific uptake and quantification of MRI-detectable nanoparticles or PET-detectable radiotracers. Particular molecular signatures can be leveraged to target anti-inflammatory TAM, which support tumor growth, and pro-inflammatory TAM, which suppress tumor growth. In addition, TAM-directed imaging probes can be designed to include immune modulating properties, thereby leading to combined diagnostic and therapeutic (theranostic) effects. In this review, we will discuss the complementary role of TAM-directed radiotracers and iron oxide nanoparticles for monitoring cancer immunotherapies with PET and MRI technologies. In addition, we will outline how TAM-directed imaging and therapy is interdependent and can be connected towards improved clinical outcomes

show abstract

Section: Monitoring Cancer Immunotherapy With Iron Oxide Nanoparticlesmentioning

confidence: 98%

The yin and yang of imaging tumor associated macrophages with PET and MRI

Mukherjee¹,

Sonanini²,

Maurer³

et al. 2019

Theranostics

View full text Add to dashboard Cite

show abstract

“…This was found to correlate with elevated TAM quantities, and it was presumed that increased tumour clearance was achieved by turning TAM-related "eat me" signals on (doxorubicin) and "do not eat me" signals off (CD47 mAb). [412]. This combination could be useful in increasing doxorubicin efficacy in a clinical setting as well.…”

Section: Mechanisms Underlying Drug Efficacy/synergymentioning

confidence: 99%

Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies

Lilienthal

Herold

2020

IJMS

173

130

View full text Add to dashboard Cite

Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Due to micrometastatic spread, radical surgery alone rarely results in cure. Introduction of combination chemotherapy in the 1970s, however, dramatically increased overall survival rates from 20% to approximately 70%. Unfortunately, large clinical trials aiming to intensify treatment in the past decades have failed to achieve higher cure rates. In this review, we revisit how the heterogenous nature of osteosarcoma as well as acquired and intrinsic resistance to chemotherapy can account for stagnation in therapy improvement. We summarise current osteosarcoma treatment strategies focusing on molecular determinants of treatment susceptibility and resistance. Understanding therapy susceptibility and resistance provides a basis for rational therapy betterment for both identifying patients that might be cured with less toxic interventions and targeting resistance mechanisms to sensitise resistant osteosarcoma to conventional therapies.

show abstract

“…Conversely, when the SIRPa is blocked, TAMs portend a M1 phenotype (133). Previous work in experimental models of hematologic and solid malignancies have identified CD47 and SIRPa as potential therapeutic targets, whereby blocking this axis (predominantly using anti-CD47 mAb) demonstrated increased phagocytosis of cancer cells by macrophages (2,4,5,126,128,134) and M1 polarization (131). Increased phagocytosis of human RMS cells was observed in vitro when macrophages were treated with anti-CD47 monoclonal antibody (4).…”

Section: "Don't Eat-me" Receptorsmentioning

confidence: 99%

“…Increased phagocytosis of human RMS cells was observed in vitro when macrophages were treated with anti-CD47 monoclonal antibody (4). In murine studies of osteosarcoma, CD47 blockade decreased tumor progression, increased macrophage infiltration into the tumor, and increased overall survival (2,5). Currently, there are no open clinical trials targeting the CD47-SIRPa pathway for pediatric sarcomas.…”

Section: "Don't Eat-me" Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

Targeting Tumor-Associated Macrophages in the Pediatric Sarcoma Tumor Microenvironment

et al. 2020

View full text Add to dashboard Cite

For many pediatric sarcoma patients, multi-modal therapy including chemotherapy, radiation, and surgery is sufficient to cure their disease. However, event-free and overall survival rates for patients with more advanced disease are grim, necessitating the development of novel therapeutic approaches. Within many pediatric sarcomas, the normal immune response, including recognition and destruction of cancer cells, is lost due to the highly immune suppressive tumor microenvironment (TME). In this setting, tumor cells evade immune detection and capitalize on the immune suppressed microenvironment, leading to unchecked proliferation and metastasis. Recent preclinical and clinical approaches are aimed at understanding this immune suppressive microenvironment and employing cancer immunotherapy in an attempt to overcome this, by renewing the ability of the immune system to recognize and destroy cancer cells. While there are several factors that drive the attenuation of immune responses in the sarcoma TME, one of the most remarkable are tumor associated macrophage (TAMs). TAMs suppress immune cytolytic function, promote tumor growth and metastases, and are generally associated with a poor prognosis in most pediatric sarcoma subtypes. In this review, we summarize the mechanisms underlying TAM-facilitated immune evasion and tumorigenesis and discuss the potential therapeutic application of TAM-focused drugs in the treatment of pediatric sarcomas.

show abstract

Improving the efficacy of osteosarcoma therapy: combining drugs that turn cancer cell ‘don't eat me’ signals off and ‘eat me’ signals on

Cited by 32 publications

References 50 publications

The yin and yang of imaging tumor associated macrophages with PET and MRI

The yin and yang of imaging tumor associated macrophages with PET and MRI

Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies

Targeting Tumor-Associated Macrophages in the Pediatric Sarcoma Tumor Microenvironment

Contact Info

Product

Resources

About