Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives

Personeni, Nicola; Smiroldo, Valeria; Giunta, Emilio Francesco; Prete, Maria Giuseppina; Rimassa, Lorenza; Bregni, Giacomo; Sclafani, Francesco

doi:10.3390/cancers13184506

Cited by 14 publications

(13 citation statements)

References 121 publications

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“…Predictive biomarkers are frequently used to identify high-risk patients and predict drug responses. Until now, several potential prognostic biomarkers have been discovered [27][28][29], but there were still no suitable molecular biomarkers applied in the clinic. The findings of our study suggested that FOCAD and its ubiquitination might be used to predict the outcomes of CRC patients.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of ubiquitinome of human colorectal cancer and identification of potential survival-related ubiquitination

et al. 2022

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Background According to the Global Cancer Statistics in 2020, the incidence and mortality of colorectal cancer (CRC) rank third and second among all tumors. The disturbance of ubiquitination plays an important role in the initiation and development of CRC, but the ubiquitinome of CRC cells and the survival-relevant ubiquitination are poorly understood. Methods The ubiquitinome of CRC patients (n = 6) was characterized using our own data sets of proteomic and ubiquitin-proteomic examinations. Then, the probable survival-relevant ubiquitination was searched based on the analyses of data sets from public databases. Results For the ubiquitinomic examination, we identified 1690 quantifiable sites and 870 quantifiable proteins. We found that the highly-ubiquitinated proteins (n ≥ 10) were specifically involved in the biological processes such as G-protein coupling, glycoprotein coupling, and antigen presentation. Also, we depicted five motif sequences frequently recognized by ubiquitin. Subsequently, we revealed that the ubiquitination content of 1172 proteins were up-regulated and 1700 proteins were down-regulated in CRC cells versus normal adjacent cells. We demonstrated that the differentially ubiquitinated proteins were relevant to the pathways including metabolism, immune regulation, and telomere maintenance. Then, integrated with the proteomic datasets from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 98), we revealed that the increased ubiquitination of FOCAD at Lys583 and Lys587 was potentially associated with patient survival. Finally, we depicted the mutation map of FOCAD and elucidated its potential functions on RNA localization and translation in CRC. Conclusions The findings of this study described the ubiquitinome of CRC cells and identified abnormal ubiquitination(s) potentially affecting the patient survival, thereby offering new probable opportunities for clinical treatment.

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Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of ubiquitinome of human colorectal cancer and identification of potential survival-related ubiquitination

et al. 2022

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“…Several clinical trials investigating panitumumab rechallenge or reintroduction are ongoing ( Table 2 ), including VELO (EudraCT Number 2018-001600-12) ( 65 ). The VELO trial, a randomized, multicenter phase II trial, is comparing panitumumab plus TAS-102 (trifluridine/tipiracil) vs TAS-102 as third-line treatment in 112 patients with RAS wt mCRC, who had achieved PR or CR in first-line treatment with anti-EGFR therapy; the primary endpoint is PFS, while secondary endpoints include OS and ORR ( 65 , 71 ).…”

Section: Clinical Evidence For Rechallenge With Anti-egfr Therapymentioning

confidence: 99%

Rechallenge with anti-EGFR therapy to extend the continuum of care in patients with metastatic colorectal cancer

et al. 2023

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In patients with RAS wild-type metastatic colorectal cancer (mCRC), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody plus chemotherapy is a standard option for treatment in the first-line setting. Patients who progress while on treatment with anti-EGFR-based therapy can be resistant to further anti-EGFR treatment, but evidence suggests that the anti-EGFR-resistant clones decay, thereby opening the potential for rechallenge or reintroduction in later lines of treatment. Results from recent clinical studies have shown that some patients with mCRC who are rechallenged with anti-EGFR monoclonal antibodies exhibit durable responses. While other therapies have demonstrated improved overall survival in chemorefractory mCRC over the past decade, rechallenge with anti-EGFR monoclonal antibodies in later lines of treatment represents a new option that deserves further investigation in clinical trials. In this review, we summarize the molecular rationale for rechallenge or reintroduction in patients with mCRC who have progressed on earlier-line anti-EGFR treatment and examine the current evidence for using liquid biopsy as a method for selecting rechallenge as a therapeutic option. We also provide an overview of published trials and trials in progress in this field, and outline the potential role of rechallenge in the current clinical setting.

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“…Widely used bevacizumab can bind specifically to vascular endothelial growth factor (VEGFR) to inhibit tumor metastasis by reducing microvascular growth. As a current systemic therapy, regorafenib [ 72 ] is an oral multi-kinase inhibitor targeting the VEGFR and the tumor microenvironment. Tyrosine kinase inhibitors have been shown to be one of the effective drugs in tumor treatment, not only promoting the stromal to epithelial phenotype [ 14 ], but also inhibiting tumor invasion and metastasis.…”

Section: Targeted Therapy Associated With Emtmentioning

confidence: 99%

Current Progress of EMT: A New Direction of Targeted Therapy for Colorectal Cancer with Invasion and Metastasis

Tan

Sun

et al. 2022

Biomolecules

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Colorectal cancer (CRC) is a common malignant tumor with a high frequency of recurrence and metastasis, which are the major causes of death in patients. The prerequisite for the invasion and metastasis is the strong mobility of CRC cells to transport far away from the original site to the distant organs and tissues, where they settle down and proliferate. It was reported that the epithelial-mesenchymal transition (EMT) is involved in the occurrence and development of various tumors in the entire process of tumor invasion and metastasis. Therefore, as a vital factor for the biological characteristics of tumor cells, EMT markers may serve as prognostic predictors and potential therapeutic targets in CRC. This article mainly reviews the current status of CRC with metastasis, the studies of EMT, the possible relationship of EMT with CRC, as well as the potential targeted therapy.

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Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives

Cited by 14 publications

References 121 publications

Comprehensive characterization of ubiquitinome of human colorectal cancer and identification of potential survival-related ubiquitination

Comprehensive characterization of ubiquitinome of human colorectal cancer and identification of potential survival-related ubiquitination

Rechallenge with anti-EGFR therapy to extend the continuum of care in patients with metastatic colorectal cancer

Current Progress of EMT: A New Direction of Targeted Therapy for Colorectal Cancer with Invasion and Metastasis

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