Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy

Casadei-Gardini, Andrea; Passardi, Alessandro; Fornaro, Lorenzo; Rosetti, Paola; Valgiusti, Martina; Ruscelli, Silvia; Monti, Manuela; Casadei, Chiara; Pagan, Flavia; Frassineti, Giovanni Luca

doi:10.1016/j.critrevonc.2018.01.007

Cited by 9 publications

(4 citation statements)

References 34 publications

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“…Toxicity was deemed unacceptable and led to early discontinuation in two of these trials and also showed poor long‐term efficacy results . Other studies with cetuximab‐chemoradiation did not support further clinical development in phase III trials of cetuximab in patients with SCCAC, either due to small numbers, excessive toxicity or incomplete/inconclusive efficacy data . It should be noted that those studies testing cetuximab were conducted mainly with cisplatin‐5FU as a chemotherapy partner .…”

Section: Discussionmentioning

confidence: 99%

VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

et al. 2019

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Section: Discussionmentioning

confidence: 99%

VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

et al. 2019

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“…KRT5 (CV of 333 samples: 0.083) and TP63 (CV of 333 samples: 0.069), as known SCC diagnostic markers 25 , showed a high and ubiquitous expression level among all SCCs. EGFR and CD274 (PDL1), serve as limited therapeutic targets for SCCs 38 – 42 , presented similar expression level across all SCCs. Frequently copy-number gain gene AKT1 expressed ubiquitously (CV of 333 samples: 0.060) in all cases, whereas YAP1 , AKT3 , and SOX2 exhibited different extent loss of expression on protein level (AKT1, YAP1, AKT3, and SOX2), indicating differentially activated signaling in 17 SCCs.…”

Section: Resultsmentioning

confidence: 99%

Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas across multiple tissues

et al. 2022

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Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are two main histological subtypes of solid cancer; however, SCCs are derived from different organs with similar morphologies, and it is challenging to distinguish the origin of metastatic SCCs. Here we report a deep proteomic analysis of 333 SCCs of 17 organs and 69 ACs of 7 organs. Proteomic comparison between SCCs and ACs identifies distinguishable pivotal pathways and molecules in those pathways play consistent adverse or opposite prognostic roles in ACs and SCCs. A comparison between common and rare SCCs highlights lipid metabolism may reinforce the malignancy of rare SCCs. Proteomic clusters reveal anatomical features, and kinase-transcription factor networks indicate differential SCC characteristics, while immune subtyping reveals diverse tumor microenvironments across and within diagnoses and identified potential druggable targets. Furthermore, tumor-specific proteins provide candidates with differentially diagnostic values. This proteomics architecture represents a public resource for researchers seeking a better understanding of SCCs and ACs.

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“…EGFR signaling modulates diverse cell functions and promotes cellular proliferation, differentiation, migration, growth, and survival [53]. Mutations in EFGR lead to its overexpression (upregulation or amplification), which is associated with many cancers, including lung cell carcinoma [54], glioblastoma [55], anal cancer [56], and epithelial tumors in the head and neck [57]. Previous studies have indicated that EGFR activation plays a pivotal role in the development of HCC [58, 59]; however, there is no evidence to support the downregulation of EGFR expression by RSM.…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae

et al. 2019

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Background Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. Methods In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC. Results In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice. Conclusions We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC. Electronic supplementary material The online version of this article (10.1186/s13020-019-0249-6) contains supplementary material, which is available to authorized users.

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Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy

Cited by 9 publications

References 34 publications

VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas across multiple tissues

A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae

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