Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer

Rizzo, Giulia; Bertotti, Andrea; Leto, Simonetta M.; Vetrano, Stefania

doi:10.1186/s13046-021-01970-2

Cited by 30 publications

(37 citation statements)

References 188 publications

(272 reference statements)

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“…Among digestive cancers, colorectal cancer (CRC) represents the third most common cancer world-wide and the third highest cause of cancer-related mortality, which is responsible of about 10% of total cancer death [ 26 ]. CRC development resulted from the transformation of normal epithelium to adenoma and then adenocarcinoma.…”

Section: Orexins and Digestive Cancersmentioning

confidence: 99%

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

et al. 2021

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Over 20 years ago, orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus were identified. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role. The present review summarizes the relationship between cancers and orexins/OX1R system as an emerging target.

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Section: Orexins and Digestive Cancersmentioning

confidence: 99%

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

et al. 2021

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“…However, PDX models are promising tools for translational research. PDX models have been used for various types of cancer research such as drug evaluation, precision oncology, biomarker detection for drug sensitivity or resistance, and comprehension of tumor behavior [16,17,80,81]. For example, Berotti et al found that amplification of the Erb-B2 receptor tyrosine kinase 2 (ERBB2) gene is a determinant of driver of cetuximab resistance and predicts the response to epidermal growth factor receptor (EGFR) and HER-2-targeted therapies in a colon cancer PDX model [3].…”

Section: Translational Applications Of Pdx Modelsmentioning

confidence: 99%

“…A large PDX cohort could cover almost every stage and grade of histological subtype. Furthermore, clinical information, such as prognosis and drug sensitivity, can also be recorded [14][15][16][17]. Briefly, all materials and information from cancer patients and PDX models are stored in biobanks and data banks.…”

Section: Introductionmentioning

confidence: 99%

“…The information also includes data, such as clinicopathological findings, genomic analysis findings, and drug sensitivity data. These materials and information in biobanks or databanks are intended for use in precision medicine and development of anticancer agents; this platform allows many researchers to share all types of information and conduct experiments with PDX that reflect the characteristics of the primary tumor (Figure 1) [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review

Tanaka

Nishie

Ueda

et al. 2021

IJMS

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Background: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX. Methods: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines. Results: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model. Conclusion: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.

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“…In this model, the patient’s tumor is mechanically and/or enzymatically treated, and then, the cells are incorporated into Matrigel to generate a 3D model. The PDOs can be maintained in culture and/or can be injected into immunocompromised mice [ 73 ]. These models are gaining presence in molecular oncology studies, particularly in the case of solid tumors, and may constitute an ex vivo 3D model closer to the tumor environment.…”

Section: Preclinical Models Of Adc Resistancementioning

confidence: 99%

Generation of Antibody-Drug Conjugate Resistant Models

Gandullo-Sánchez

Ocaña

Pandiella

2021

Cancers

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In the last 20 years, antibody-drug conjugates (ADCs) have been incorporated into the oncology clinic as treatments for several types of cancer. So far, the Food and Drug Administration (FDA) has approved 11 ADCs and other ADCs are in the late stages of clinical development. Despite the efficacy of this type of drug, the tumors of some patients may result in resistance to ADCs. Due to this, it is essential not only to comprehend resistance mechanisms but also to develop strategies to overcome resistance to ADCs. To reach these goals, the generation and use of preclinical models to study those mechanisms of resistance are critical. Some cells or patient tumors may result in primary resistance to the action of an ADC, even if they express the antigen against which the ADC is directed. Isolated primary tumoral cells, cell lines, or patient explants (patient-derived xenografts) with these characteristics can be used to study primary resistance. The most common method to generate models of secondary resistance is to treat cancer cell lines or tumors with an ADC. Two strategies, either continuous treatment with the ADC or intermittent treatment, have successfully been used to develop those resistance models.

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Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer

Cited by 30 publications

References 188 publications

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review

Generation of Antibody-Drug Conjugate Resistant Models

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