Advances in the development of chordoma models for drug discovery and precision medicine

Walker, Robert L.; Hornicek, Francis J.; Duan, Zhenfeng

doi:10.1016/j.bbcan.2022.188812

Cited by 4 publications

(8 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The functional validation of new therapeutic targets and strategies resulting from multi-omics studies requires appropriate patient-derived samples and preclinical models. To this end, a variety of chordoma models have been developed by several groups (105,106). In addition, the Chordoma Foundation has built a tumor biobank of over 500 biospecimens and a model repository currently consisting of 26 cell lines, 12 patient-derived xenograft (PDX) models, and a PBMC-humanized mouse model (www.chordoma.org/research).…”

Section: Recent Advances In the Establishment And Availability Of Cho...mentioning

confidence: 99%

Emerging target discovery and drug repurposing opportunities in chordoma

Freed

Sommer²,

Punturi³

2022

Front. Oncol.

View full text Add to dashboard Cite

The development of effective and personalized treatment options for patients with rare cancers like chordoma is hampered by numerous challenges. Biomarker-guided repurposing of therapies approved in other indications remains the fastest path to redefining the treatment paradigm, but chordoma’s low mutation burden limits the impact of genomics in target discovery and precision oncology efforts. As our knowledge of oncogenic mechanisms across various malignancies has matured, it’s become increasingly clear that numerous properties of tumors transcend their genomes – leading to new and uncharted frontiers of therapeutic opportunity. In this review, we discuss how the implementation of cutting-edge tools and approaches is opening new windows into chordoma’s vulnerabilities. We also note how a convergence of emerging observations in chordoma and other cancers is leading to the identification and evaluation of new therapeutic hypotheses for this rare cancer.

show abstract

Section: Recent Advances In the Establishment And Availability Of Cho...mentioning

confidence: 99%

Emerging target discovery and drug repurposing opportunities in chordoma

Freed

Sommer²,

Punturi³

2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Precision medicine has been covering various areas ranging from drug discovery, design, and development, the analysis of drug sensitivity in pharmacology, and the construction of clinical decision support systems in health analytics to a better understanding of several diseases and their relationships with genes, family history, and other attributable factors in medicine [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

A hybrid algorithm for clinical decision support in precision medicine based on machine learning

Zhang

Lin

2023

BMC Bioinformatics

View full text Add to dashboard Cite

Purpose The objective of the manuscript is to propose a hybrid algorithm combining the improved BM25 algorithm, k-means clustering, and BioBert model to better determine biomedical articles utilizing the PubMed database so, the number of retrieved biomedical articles whose content contains much similar information regarding a query of a specific disease could grow larger. Design/methodology/approach In the paper, a two-stage information retrieval method is proposed to conduct an improved Text-Rank algorithm. The first stage consists of employing the improved BM25 algorithm to assign scores to biomedical articles in the database and identify the 1000 publications with the highest scores. The second stage is composed of employing a method called a cluster-based abstract extraction to reduce the number of article abstracts to match the input constraints of the BioBert model, and then the BioBert-based document similarity matching method is utilized to obtain the most similar search outcomes between the document and the retrieved morphemes. To realize reproducibility, the written code is made available on https://github.com/zzc1991/TREC_Precision_Medicine_Track. Findings The experimental study is conducted based on the data sets of TREC2017 and TREC2018 to train the proposed model and the data of TREC2019 is used as a validation set confirming the effectiveness and practicability of the proposed algorithm that would be implemented for clinical decision support in precision medicine with a generalizability feature. Originality/value This research integrates multiple machine learning and text processing methods to devise a hybrid method applicable to domains of specific medical literature retrieval. The proposed algorithm provides a 3% increase of P@10 than that of the state-of-the-art algorithm in TREC 2019.

show abstract

“…Chordoma is a rare bone tumour with an incidence of 0.08 cases per 100,000 individuals and a median age at diagnosis of 50–60 years [ 1 , 2 ] arising from undifferentiated remnants of the embryonic notochord. Chordomas are mainly located in the skull base and sacrococcygeal region and comprise different histotypes, including conventional, chondroid, dedifferentiated and poorly differentiated chordomas [ 2 , 3 , 4 ]. The most common type, the conventional chordoma, is characterized by cords and nests of large epithelioid cells with clear to light eosinophilic vacuolated cytoplasm (physaliphorous cells) within an extracellular abundant myxoid matrix.…”

Section: Introductionmentioning

confidence: 99%

“…Dedifferentiated chordoma exhibits a biphasic phenotype with areas of conventional chordoma along with areas of high-grade sarcomatous features composed of spindle and pleomorphic cells. Poorly differentiated chordoma is a rare histotype arising mainly in children and young adults and composed of nests of mitotically active epithelioid cells with scattered intracytoplasmic vacuoles lacking physaliphorous cell morphology and extracellular myxoid stroma and characterized by SMARCB1 homozygous deletion and loss of INI1 expression [ 3 , 4 , 5 ]. The latter two histotypes are considered the most aggressive histotypes.…”

Section: Introductionmentioning

confidence: 99%

“…The first-line treatment is based on surgical resection of the tumour, which together with the tumour stage at the diagnosis, is one of the major prognostic factors [ 2 ]. Generally, five-year overall age-adjusted relative survival is estimated to be approximately 61% [ 2 ], while the recurrence rate is 43–85% [ 4 ]. Thus, it is of paramount importance to develop new therapeutic strategies, which greatly depend on both histological and molecular features [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line

Pagani

Gryzik

Somenza

et al. 2023

JPM

View full text Add to dashboard Cite

Chordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to different histotypes and molecular alterations, including TBXT duplication and SMARCB1 homozygous deletion. Partial or complete PTEN deficiency has also been observed. PTEN is a negative regulator of the Akt/mTOR pathway and hyperactivation of Akt/mTOR in cells lacking PTEN expression contributes to cell proliferation and invasiveness. This pathway is targeted by mTOR inhibitors and the availability of in vitro models of chordoma cells will aid in further investigating this issue. However, isolation and maintenance of chordoma cell lines are challenging and PTEN-deleted chordoma cell lines are exceedingly rare. Hereby, we established and characterized a novel human PTEN-deleted chordoma cell line (CH3) from a primary skull base chordoma. Cells exhibited morphological and molecular features of the parent tumour, including PTEN loss and expression of Brachyury and EMA. Moreover, we investigated the activation of the mTOR pathway and cell response to mTOR inhibitors. CH3 cells were sensitive to Rapamycin treatment suggesting that mTOR inhibitors may represent a valuable option for patients suffering from PTEN-deleted chordomas.

show abstract

Advances in the development of chordoma models for drug discovery and precision medicine

Cited by 4 publications

References 82 publications

Emerging target discovery and drug repurposing opportunities in chordoma

Emerging target discovery and drug repurposing opportunities in chordoma

A hybrid algorithm for clinical decision support in precision medicine based on machine learning

Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line

Contact Info

Product

Resources

About