Biology and Therapeutic Targets of Colorectal Serrated Adenocarcinoma; Clues for a Histologically Based Treatment against an Aggressive Tumor

Alburquerque-González, Begoña; López-Calderón, Fernando; López-Abellán, María Dolores; Esteban-Gil, Ángel; García‐Solano, José; Conesa‐Zamora, Pablo

doi:10.3390/ijms21061991

Cited by 8 publications

(2 citation statements)

References 115 publications

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“…Furthermore, organoids have been suggestively to hone its capacity in modelling different cancer subtypes with the help of genetic engineering technology. Serrated CRC, for example, represents an aggressive subtype of CRC with often relative resistance to anti-EGFR therapy and poor prognosis [ 73 ]. The organoids with clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) which incorporate common genetic alterations [ Kras or B-Raf proto-oncogene ( BRAF )] revealed a specific tumor niche and prognostic gene markers representing human serrated CRC [ 74 , 153 ].…”

Section: Application Of Spheroids and Organoids For Drug Screeningmentioning

confidence: 99%

Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening

Ahmad Zawawi,

Salleh,

Musa

2024

Exploration of Targeted Anti-Tumor Therapy

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Colorectal cancer (CRC) is a heterogeneous disease. Conventional two-dimensional (2D) culture employing cell lines was developed to study the molecular properties of CRC in vitro. Although these cell lines which are isolated from the tumor niche in which cancer develop, the translation to human model such as studying drug response is often hindered by the inability of cell lines to recapture original tumor features and the lack of heterogeneous clinical tumors represented by this 2D model, differed from in vivo condition. These limitations which may be overcome by utilizing three-dimensional (3D) culture consisting of spheroids and organoids. Over the past decade, great advancements have been made in optimizing culture method to establish spheroids and organoids of solid tumors including of CRC for multiple purposes including drug screening and establishing personalized medicine. These structures have been proven to be versatile and robust models to study CRC progression and deciphering its heterogeneity. This review will describe on advances in 3D culture technology and the application as well as the challenges of CRC-derived spheroids and organoids as a mode to screen for anticancer drugs.

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Section: Application Of Spheroids and Organoids For Drug Screeningmentioning

confidence: 99%

Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening

Ahmad Zawawi,

Salleh,

Musa

2024

Exploration of Targeted Anti-Tumor Therapy

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“…However, given the fact that SAC, compared to conventional colorectal carcinoma, exhibits a higher frequency of KRAS or BRAF mutations and that most SACs are microsatellite stable [ 3 , 4 ], this CRC subtype is especially resistant to targeted therapy such as anti-EGFR and immune checkpoint inhibitors, respectively. Therefore, there is an urgent need to count with a targeted molecular therapy for treating SAC [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The FDA-Approved Antiviral Raltegravir Inhibits Fascin1-Dependent Invasion of Colorectal Tumor Cells In Vitro and In Vivo

Alburquerque-González

Bernabé‐García

Bernabé-García

et al. 2021

Cancers

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Background: Fascin1 is the key actin-bundling protein involved in cancer invasion and metastasis whose expression is associated with bad prognosis in tumor from different origins. Methods: In the present study, virtual screening (VS) was performed for the search of Fascin1 inhibitors and RAL, an FDA-approved inhibitor of human immunodeficiency virus‑1 (HIV-1) integrase, was identified as a potential Fascin1 inhibitor. Biophysical techniques including nuclear magnetic resonance (NMR) and differential scanning fluorimetry (DSF) were carried out in order to confirm RAL as a Fascin1 blocker. The effect of RAL on actin-bundling activity Fascin1 was assessed by transmission electron microscopy (TEM), immunofluorescence, migration, and invasion assays on two human colorectal adenocarcinoma cell lines: HCT-116 and DLD-1. In addition, the anti-metastatic potential of RAL was in vivo evaluated by using the zebrafish animal model. Results: NMR and DSF confirmed in silico predictions and TEM demonstrated the RAL-induced disorganization of the actin structure compared to control conditions. The protrusion of lamellipodia in cancer cell line overexpressing Fascin1 (HCT-116) was abolished in the presence of this drug. By following the addition of RAL, migration of HCT-116 and DLD-1 cell lines was significantly inhibited. Finally, using endogenous and exogenous models of Fascin1 expression, the invasive capacity of colorectal tumor cells was notably impaired in the presence of RAL in vivo assays; without undesirable cytotoxic effects. Conclusion: The current data show the in vitro and in vivo efficacy of the antiretroviral drug RAL in inhibiting human colorectal cancer cells invasion and metastasis in a Fascin1-dependent manner.

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Survival strategies: How tumor hypoxia microenvironment orchestrates angiogenesis

Yang,

Mu,

et al. 2024

Biomedicine & Pharmacotherapy

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Biology and Therapeutic Targets of Colorectal Serrated Adenocarcinoma; Clues for a Histologically Based Treatment against an Aggressive Tumor

Cited by 8 publications

References 115 publications

Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening

Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening

The FDA-Approved Antiviral Raltegravir Inhibits Fascin1-Dependent Invasion of Colorectal Tumor Cells In Vitro and In Vivo

Survival strategies: How tumor hypoxia microenvironment orchestrates angiogenesis

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