Shedding light on emerging therapeutic targets for chordoma

Martinez Moreno, Margot; Wang, Elaina; Schroeder, Christian; Sullivan, Patricia; Gokaslan, Ziya

doi:10.1080/14728222.2023.2248382

Cited by 2 publications

(2 citation statements)

References 89 publications

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“…Chordoma possesses diverse genetic, epigenetic, and immunotherapeutic targets that may be a target for combinatorial therapies ( 164 ), which will need the appropriate models, from in vitro to the different animal models to test those therapies. In summary, immunocompromised mice are useful for studying tumor growth and responses to treatment independently of the immune system interference, while humanized mice provide a platform to study the interactions between human tumors and the human tumor immune microenvironment (Summarized in Table 2 ).…”

Section: Humanized Mice and Chordoma Researchmentioning

confidence: 99%

Animal model considerations for chordoma research: reproducing the tumor microenvironment in vivo with humanized mice

Campilan,

Schroeder,

Sagaityte

et al. 2024

Front. Oncol.

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Animal models have been commonly used in immunotherapy research to study the cell response to external agents and to assess the effectiveness and safety of new therapies. Over the past few decades, immunocompromised (also called immunodeficient) mice allowed researchers to grow human tumor cells without the impact of the host’s immune system. However, while this model is very valuable to understand the tumor biology and to understand the underlying mechanism of immunotherapy, the results may not always directly translate to humans. The tumor microenvironment has significant implications for tumor engraftment, growth, invasion, etc., and the immune system plays a critical role in shaping the tumor microenvironment. Human immunocompetent mice, also named humanized mice, are engineered mice that possess functional human immune cells. This in vivo model can be used to effectively study the effect of the human immune system to a human implanted tumor. Moreover, this can effectively mimic the response to treatment. This section is an overview of the current understanding of the different humanized mice that could be utilized to mimic the tumor microenvironment in chordoma.

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Section: Humanized Mice and Chordoma Researchmentioning

confidence: 99%

Animal model considerations for chordoma research: reproducing the tumor microenvironment in vivo with humanized mice

Campilan,

Schroeder,

Sagaityte

et al. 2024

Front. Oncol.

Self Cite

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“…The rich interplay of genetic alterations and signaling pathways uncovered by these studies provides a roadmap for the development of innovative and targeted interventions. The promise lies not only in treating chordomas more effectively but also in mitigating potential side effects by precisely targeting cancer cells while sparing healthy tissues [22,24,[26][27][28][29][30]47,[53][54][55][56].…”

Section: Genomic Insights Informing Targeted Approachesmentioning

confidence: 99%

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

Agosti,

Antonietti,

Zeppieri

et al. 2024

JCM

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Background: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “chordomas”, “molecular biology”, “gene aberrations”, and “target therapies”. The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results: Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral (n = 8, 44.4%), followed by clivus (n = 7, 38.9%) and lumbar spine (n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery (n = 10, 55.6%), RT (n = 9, 50.0%), and systemic treatments (n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions: This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.

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Shedding light on emerging therapeutic targets for chordoma

Cited by 2 publications

References 89 publications

Animal model considerations for chordoma research: reproducing the tumor microenvironment in vivo with humanized mice

Animal model considerations for chordoma research: reproducing the tumor microenvironment in vivo with humanized mice

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

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