Peritoneal metastasis of colorectal cancer (pmCRC): identification of predictive molecular signatures by a novel preclinical platform of matching pmCRC PDX/PD3D models

Dahlmann, Mathias; Gambara, Guido; Brzezicha, Bernadette; Popp, Oliver; Pachmayr, Eva; Wedeken, Lena; Pflaume, Alina; Mokritzkij, Margarita; Gül‐Klein, Safak; Brandl, Andreas; Schweiger-Eisbacher, Caroline; Mertins, Philipp; Hoffmann, Jens; Keilholz, Ulrich; Walther, Wolfgang; Regenbrecht, Christian; Rau, Beate; Stein, Ulrike

doi:10.1186/s12943-021-01430-7

Cited by 8 publications

(7 citation statements)

References 28 publications

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“…Analogous to the above involving the patient metastasis expression compendium dataset, we assembled a compendium dataset of PDX tumors representing over 18 major cancer types (based on tissue of origin) and 14 individual studies ( Table S1 ). 11 , 12 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 We identified the above studies and associated expression datasets by searching the GEO database. In addition, we incorporated an expression profiling dataset from Sun et al.…”

Section: Methodsmentioning

confidence: 99%

Pan-cancer molecular subtypes of metastasis reveal distinct and evolving transcriptional programs

Zhang¹,

Chen²,

Creighton³

2023

Cell Reports Medicine

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Section: Methodsmentioning

confidence: 99%

Pan-cancer molecular subtypes of metastasis reveal distinct and evolving transcriptional programs

Zhang¹,

Chen²,

Creighton³

2023

Cell Reports Medicine

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“…Data from the ONCOTRACK project confirm this hypothesis at least in part, as strong sensitivity to the SoC chemotherapies 5-FU or irinotecan has been observed in 4 out these 5 models [ 2 ]. A combination of chemotherapy with a PARP inhibitor has recently shown activity in preclinical models of peritoneal metastases of colorectal cancer with a similar molecular profile [ 23 ] and might be an alternative opportunity for this subgroup of patients. Currently, immunotherapy is evaluated as a therapeutic option in these subtypes [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Modeling of Personalized Treatments in Colon Cancer Based on Preclinical Genomic and Drug Sensitivity Data

Keil

Conrad

Becker

et al. 2021

Cancers

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The current standard therapies for advanced, recurrent or metastatic colon cancer are the 5-fluorouracil and oxaliplatin or irinotecan schedules (FOxFI) +/− targeted drugs cetuximab or bevacizumab. Treatment with the FOxFI cytotoxic chemotherapy regimens causes significant toxicity and might induce secondary cancers. The overall low efficacy of the targeted drugs seen in colon cancer patients still is hindering the substitution of the chemotherapy. The ONCOTRACK project developed a strategy to identify predictive biomarkers based on a systems biology approach, using omics technologies to identify signatures for personalized treatment based on single drug response data. Here, we describe a follow-up project focusing on target-specific drug combinations. Background for this experimental preclinical study was that, by analyzing the tumor growth inhibition in the PDX models by cetuximab treatment, a broad heterogenic response from complete regression to tumor growth stimulation was observed. To provide confirmation of the hypothesis that drug combinations blocking alternatively activated oncogenic pathways may improve therapy outcomes, 25 models out of the well-characterized ONCOTRACK PDX panel were subjected to treatment with a drug combination scheme using four approved, targeted cancer drugs.

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“… 46 Dahlmann et al established PDX models from CRC peritoneal metastasis and characterized their molecular features and responses to targeted therapies. 55 Cho et al established PDX models from CRC primary lesions and metastases and compared their responses to drugs. They discovered that metastasis-derived PDX models respond to targeted therapies differently, possibly resulting from subclonal mutations acquired during tumor metastasis.…”

Section: Pdx Models: Strengths and Weaknessesmentioning

confidence: 99%

Patient-derived xenograft models in cancer therapy: technologies and applications

Liu

Cai

et al. 2023

Sig Transduct Target Ther

111

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Patient-derived xenograft (PDX) models, in which tumor tissues from patients are implanted into immunocompromised or humanized mice, have shown superiority in recapitulating the characteristics of cancer, such as the spatial structure of cancer and the intratumor heterogeneity of cancer. Moreover, PDX models retain the genomic features of patients across different stages, subtypes, and diversified treatment backgrounds. Optimized PDX engraftment procedures and modern technologies such as multi-omics and deep learning have enabled a more comprehensive depiction of the PDX molecular landscape and boosted the utilization of PDX models. These irreplaceable advantages make PDX models an ideal choice in cancer treatment studies, such as preclinical trials of novel drugs, validating novel drug combinations, screening drug-sensitive patients, and exploring drug resistance mechanisms. In this review, we gave an overview of the history of PDX models and the process of PDX model establishment. Subsequently, the review presents the strengths and weaknesses of PDX models and highlights the integration of novel technologies in PDX model research. Finally, we delineated the broad application of PDX models in chemotherapy, targeted therapy, immunotherapy, and other novel therapies.

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Peritoneal metastasis of colorectal cancer (pmCRC): identification of predictive molecular signatures by a novel preclinical platform of matching pmCRC PDX/PD3D models

Cited by 8 publications

References 28 publications

Pan-cancer molecular subtypes of metastasis reveal distinct and evolving transcriptional programs

Pan-cancer molecular subtypes of metastasis reveal distinct and evolving transcriptional programs

Modeling of Personalized Treatments in Colon Cancer Based on Preclinical Genomic and Drug Sensitivity Data

Patient-derived xenograft models in cancer therapy: technologies and applications

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