Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers

Hwang, Kyusang; Yoon, Jin hwan; Lee, Ji Hyun; Lee, Sukmook

doi:10.3390/biomedicines9010039

Cited by 23 publications

(14 citation statements)

References 178 publications

(186 reference statements)

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“…Many of these inhibitors are being investigated in phase II clinical studies in CRC, while the US FDA has approved several drugs for targeted therapy in clinical application, as listed in Table 2 . These small molecule inhibitors and monoclonal antibodies can be used as monotherapy or combined with conventional therapies to increase the therapeutic efficacy and cancer specificity ( To et al, 2020 ; Hwang et al, 2021 ). For instance, cetuximab and panitumumab are monoclonal antibodies that target EGFR and can be used as monotherapy or combined with chemotherapy to treat patients with RAS wild-type metastatic CRC ( Hayashi et al, 2017 ; Garcia-Foncillas et al, 2019 ).…”

Section: Targeting Colorectal Cancer Metabolismmentioning

confidence: 99%

The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer

et al. 2021

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Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Metabolic reprogramming represents an important cancer hallmark in CRC. Reprogramming core metabolic pathways in cancer cells, such as glycolysis, glutaminolysis, oxidative phosphorylation, and lipid metabolism, is essential to increase energy production and biosynthesis of precursors required to support tumor initiation and progression. Accumulating evidence demonstrates that activation of oncogenes and loss of tumor suppressor genes regulate metabolic reprogramming through the downstream signaling pathways. Protein kinases, such as AKT and c-MYC, are the integral components that facilitate the crosstalk between signaling pathways and metabolic pathways in CRC. This review provides an insight into the crosstalk between signaling pathways and metabolic reprogramming in CRC. Targeting CRC metabolism could open a new avenue for developing CRC therapy by discovering metabolic inhibitors and repurposing protein kinase inhibitors/monoclonal antibodies.

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Section: Targeting Colorectal Cancer Metabolismmentioning

confidence: 99%

The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer

et al. 2021

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“…e therapeutic effect was mainly mediated by potent ADCP induced by Kupffer cells (macrophages residing in the liver) and monocytes [30][31][32]. Although the potential of perioperative antibody treatment to prevent metastasis development has not been investigated extensively in the clinic [33], one study showed increased 7year survival and reduced overall mortality in patients with primary colorectal cancer, who were treated postoperatively with anti-EpCAM antibodies [34]. Treatment had no effect on the local recurrence of the primary tumor but reduced the occurrence of distant metastases in approximately 30% of the patients.…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells

Gruijs

Braster

Overdijk

et al. 2022

Journal of Oncology

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Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment with specific tumor-targeting monoclonal antibodies (mAb) prevented surgery-induced liver metastasis development in rats. This study investigated whether the epidermal growth factor receptor (EGFR) represents a suitable target for preoperative antibody treatment of colorectal cancer patients undergoing surgery. The majority of patients with resectable colorectal liver metastases were shown to have EGFR + CTCs. Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. Additionally, all three mAbs induced antibody-dependent cellular phagocytosis (ADCP) of tumor cells by macrophages at low antibody concentrations in vitro, independent of mutations in EGFR signaling pathways. The plasma of cetuximab-treated patients efficiently opsonized tumor cells ex vivo and induced phagocytosis. Furthermore, neither proliferation nor migration of epithelial cells was affected in vitro, supporting that wound healing will not be hampered by treatment with low anti-EGFR mAb concentrations. These data support the use of a low dose of anti-EGFR mAbs prior to resection of the tumor to eliminate CTCs without interfering with the healing of the anastomosis. Ultimately, this may reduce the risk of metastasis development, consequently improving long-term patient outcome significantly.

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“…Mutations in the KRAS gene occur early in the development of many cancers and often lead to the up-regulation of RAS proteins and their downstream effector pathways [8]. Having in mind that over expression of EGFR has been found in 80% of CRC and has been as-sociated with the progression of the malignant process and poor prognosis, it is no surprise that targeted therapy based on the application of monoclonal antibodies, such as cetuximab and panitumumab that inhibit EGFR signalling, has been shown to be very effective [9,10]. Namely, the action of these monoclonal antibodies is directed to the extracellular domain of EGFR where they block binding of a ligand, which results in a subsequent inhibition of the downstream RAS-RAF-MEK-ERK signalling pathway.…”

Section: Introductionmentioning

confidence: 99%

Mutations in the KRAS gene as a predictive biomarker of therapeutic response in patients with colorectal cancer

Jugović

Nikolić

Madić

et al. 2021

Revista Romana De Medicina De Laborator

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Introduction: Despite the important role of general KRAS mutational status in the selection of an adequate therapeutic protocol in patients with colorectal cancer (CRC), studies that focus on its specific mutations and their significance on progression of disease are scarce. This study aimed to determine the significance of specific KRAS mutations in response to standard chemotherapy protocols with oxaliplatin-based (FOLFOX 4, OXFL) in the first-line and irinotecan-based chemotherapy (FOLFIRI, IFL) in the second-line therapy, and to evaluate the correlation between these mutations and clinicopathological characteristics of CRC patients. Methods: Genomic DNA was extracted from the FFPE tumour tissue sections while the KRAS mutation test was performed by using PCR methods. Results: Prevalence of KRAS gene mutations in CRC patients was 45%. Mutated KRAS was more frequent in later stages of tumor infiltrations (P =0.0017), on the right side of the colon (P= 0.0044), and in patients who developed metastases in the first 6 months after CRC diagnosis than in patients who developed metastases after 24 months (P=0.0083). In a group of patients with a poor therapeutic response to standard chemotherapy the most frequent mutations in KRAS gene were G12D and G12V (63.88%), while in a group of patients with a good response to therapeutic protocols the most prevalent mutation was G12A (66.66%). Conclusion: Our results indicate that there was a significant difference in biological behaviour between tumours harboring different mutations in KRAS gene. Overall, mutation G12A could be a novel prognostic biomarker for CRC patients treated with standard chemotherapy.

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Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers

Cited by 23 publications

References 178 publications

The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer

The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer

Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells

Mutations in the KRAS gene as a predictive biomarker of therapeutic response in patients with colorectal cancer

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