First‐line therapy for metastatic colorectal cancer: Current perspectives and future directions

Burge, Matthew; Price, Timothy; Karapetis, Christos S.

doi:10.1111/ajco.13119

Cited by 6 publications

(4 citation statements)

References 84 publications

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“…CRC patients with synchronous metastasis at first diagnosis and those patients developing metastasis during the course of disease account often for most cancer-related deaths, because of limited treatment options [18,19,20,21,24]. Optimal treatment has not yet been defined and the majority of patients with metastatic CRC are still being managed with palliative care.…”

Section: Discussionmentioning

confidence: 99%

“…Metastatic CRC has limited treatment options and thus results in higher mortality rates compared to non-metastatic CRC [18]. The cancer cells that are able to survival in circulation, and to migrate and invade another organ, are characterized by the expression of cellular oncogenes or the loss of tumor suppressor gene function [19]. Identifying the cellular mechanisms that regulate metastasis onset may be useful to develop effective anticancer therapies.…”

Section: Introductionmentioning

confidence: 99%

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Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

Tutino

Caruso

Nunzio

et al. 2019

Cancers

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Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

Tutino

Caruso

Nunzio

et al. 2019

Cancers

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“… 1 Combination chemotherapy regimens with a fluoropyrimidine plus oxaliplatin or irinotecan (FOLFOX or FOLFIRI) remain the current standard of care in the first-line treatment of metastatic colorectal cancer (mCRC). 2 Antiepidermal growth factor receptor (EGFR) antibodies combined with fluoropyrimidine-based chemotherapy may provide further clinical benefit in left-sided RAS wild-type cancers. Antivascular endothelial growth factor (VEGF) therapy is a reasonable choice for patients with RAS wild-type right-sided tumors and RAS-mutant tumors.…”

Section: Introductionmentioning

confidence: 99%

Mutational landscape of circulating tumor DNA identifies distinct molecular features associated with therapeutic response in patients with metastatic colorectal cancer

Shi

et al. 2022

Ther Adv Med Oncol

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Background: We investigated the mutational landscape of circulating tumor DNA (ctDNA) in predicting tumor response to first-line treatment in patients with metastatic colorectal cancer (mCRC). Methods: We included 41 patients with initially unresectable mCRC, treated with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX)/5-fluorouracil/leucovorin/irinotecan (FOLFIRI) with/without bevacizumab (Bev)/cetuximab (Cet). Blood samples were prospectively collected at two timepoints: at baseline and after four cycles of first-line treatment. Mutational status of 1086 genes were studied in ctDNA by targeted next-generation sequencing (NGS). Molecular mutational burden (MMB) was defined as mean mutation frequency among obtained mutations for each gene. To evaluate the association between molecular characteristics of cfDNA and therapeutic response better, we divided these patients into MMB-high and MMB-low group according to the median value of MMB (0.3). Results: Among the 41 enrolled patients, alterations of six genes ( TRIM24, SPEN, RNF43, PRKAR1A, KRAS, and KDM5 C) were found at baseline. Baseline MMB of six genes was significantly lower in partial response (PR)/stable disease (SD) patients than progression disease (PD) patients ( p = 0.0012). Further analysis demonstrated that genomic profiling of ctDNA from pretreatment blood samples was significantly different between PR/SD (non-PD) group and PD group. By comparing the baseline levels of KRAS MMB in the two subgroups, we found that PD cases were all MMB-high, whereas non-PD cases were mainly in MMB-low subgroup. Furthermore, patients with low-KRAS MMB had superior response rate, significantly longer progression-free survival (PFS) and longer overall survival (OS) than high-KRAS MMB group. Conclusions: This prospective and serial genomic profiling study revealed the utility of ctDNA in predicting clinical outcomes in mCRC patients under first-line treatment. Levels of KRAS MMB might aid in monitoring therapeutic efficacy in mCRC patients at pretreatment/after four cycles of first-line treatment.

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“…The first-line conventional therapy for metastatic colorectal cancer is bevacizumab ( 15 ). It is a re-combined humanized monoclonal antibody directed against VEGF-A.…”

Section: Introductionmentioning

confidence: 99%

IL-6, TNF-α and IL-12p70 levels in patients with colorectal cancer and their predictive value in anti-vascular therapy

Zheng

Wang

et al. 2022

Front. Oncol.

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We aimed to analyze the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12p70) in colorectal cancer and evaluate the predictive significance of clinical efficacy of patients with colorectal cancer treated with anti-vascular therapy combined with chemotherapy. A retrospective study of 162 patients with colorectal cancer in Fujian Medical University Hospital was conducted from January 2019 to December 2020. A comparative analysis of the levels of IL-6, TNF-α and IL-12p70 between the two groups were studied. The relationship between the levels and the clinical characteristics of patients was observed; the factors affecting the levels of IL-6, TNF-α, and IL-12p70 in colorectal cancer patients were analyzed, and the predictive validity of the efficacy of anti-vascular therapy was evaluated. We observed that the individual expression levels of IL-6, TNF-α and IL-12p70 in the patients with colorectal cancer are related to lymph node metastasis, TNM staging, and degree of differentiation (P<0.05); however, they are irrelevant to the age, sex, and tumor location of patients with colorectal cancer (P>0.05). The multiple stepwise regression analysis indicates that lymph node metastasis and TNM staging are independent risk factors that correlate with IL-6 and IL-12p70 levels in colorectal cancer patients (P<0.01). The degree of differentiation was found to be an independent risk factor connected to TNF- α levels of patients with colorectal cancer. The change of IL-12p70 level could predict the validity of anti-vascular treatment for advanced colorectal cancer. When evaluated for combined expression, IL-6 and IL-12p70 in patients with colorectal cancer closely related to lymph node metastasis and TNM staging. IL-12p70 can be used as a predictor of anti-vascular therapy with colorectal cancer.

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First‐line therapy for metastatic colorectal cancer: Current perspectives and future directions

Cited by 6 publications

References 84 publications

Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

Mutational landscape of circulating tumor DNA identifies distinct molecular features associated with therapeutic response in patients with metastatic colorectal cancer

IL-6, TNF-α and IL-12p70 levels in patients with colorectal cancer and their predictive value in anti-vascular therapy

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