Cetuximab therapy in the treatment of metastatic colorectal cancer: The future frontier?

Gomez, Dhanny; Rosa, Antonella; Addison, A; Brooks, Adam; Malik, Hassan; Cameron, Iain C.

doi:10.1016/j.ijsu.2013.04.014

Cited by 11 publications

(5 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have shown the improvements in survival after the addition of anti-VEGF/EGFR[20-22]. Recently, a number of case series describing 10-year actual survivors after liver resection of CRLM have been published[23,24].…”

Section: Discussionmentioning

confidence: 99%

Resection margin influences the outcome of patients with bilobar colorectal liver metastases

Carlo¹,

Yeung²,

Mills³

et al. 2016

WJH

View full text Add to dashboard Cite

AIMTo evaluate the outcome of patients with bilobar colorectal liver metastases (CRLM) and identify clinico-pathological variables that influenced survival.METHODSPatients with bilobar CRLM were identified from a prospectively maintained hepatobiliary database during the study period (January 2010-June 2014). Collated data included demographics, primary tumour treatment, surgical data, histopathology analysis and clinical outcome. Down-staging therapy included Oxaliplatin- or Irinotecan- based regimens, and Cetuximab was also used in patients that were K-RAS wild-type. Response to neo-adjuvant therapy was assessed at the multi-disciplinary team meeting and considered for surgery if all macroscopic CRLM were resectable with a clear margin while preserving sufficient liver parenchyma.RESULTSOf the 136 patients included, thirty-two (23.5%) patients were considered inoperable and referred for palliative chemotherapy, and thirty-four (25%) patients underwent liver resection. Seventy (51.4%) patients underwent down-staging therapy, of which 37 (52.8%) patients responded sufficiently to undergo liver resection. Patients that failed to respond to down-staging therapy (n = 33, 47.1%) were referred for palliative therapy. There was a significant difference in overall survival between the three groups (surgery vs down-staging therapy vs inoperable disease, P < 0.001). All patients that underwent hepatic resection, including patients that had down-staging therapy, had a significantly better overall survival compared to patients that were inoperable (P < 0.001). On univariate analysis, only resection margin significantly influenced disease-free survival (P = 0.017). On multi-variate analysis, R0 resection (P = 0.030) and female (P = 0.036) gender significantly influenced overall survival.CONCLUSIONPatients undergoing liver resection with bilobar CRLM have a significantly better survival outcome. R0 resection is associated with improved disease-free and overall survival in this patient group.

show abstract

Section: Discussionmentioning

confidence: 99%

Resection margin influences the outcome of patients with bilobar colorectal liver metastases

Carlo¹,

Yeung²,

Mills³

et al. 2016

WJH

View full text Add to dashboard Cite

show abstract

“…Cetuximab, a chimeric mAb with approximately 152 kDa molecular weight, has a higher affinity to EGFR compared to its natural ligands, thereby inhibits the tumorigenesis effects of EGFR activation [73,74]. Cetuximab, combined with chemotherapy, is the standard practice for first-line treatment of RAS wild-type metastatic CRC patients [75].…”

Section: Cetuximabmentioning

confidence: 99%

Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer

et al. 2021

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.

show abstract

“…Patients who do not respond to this first line therapy and have wild-type KRAS gene are sometimes given the anti-EGFR (epidermal growth factor receptor) therapy, Cetuximab or Panitumumab. However, the overall survival is only 4.6% to 12.3% for Cetuximab monotherapy and 6.9% to 18.9% for Cetuximab in combination with chemotherapy for colorectal cancer, and almost all therapy recipients eventually develop resistance to this second line therapy due to the selective pressure for activating mutation of proto-oncogene KRAS, downstream of the EGFR signaling pathway (6)(7)(8). Although immune checkpoint blockade therapy has some success with microsatellite-unstable CRCs, most (80%) sporadic CRCs are microsatellite-stable and refractory to such therapy (9).…”

Section: Introductionmentioning

confidence: 99%

KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane

Lam

Low

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide. To date, chemotherapeutic treatment of advanced CRC that has metastasized has a dismayed success rate of less than 30%. Further, most (80%) sporadic CRCs are microsatellite-stable and are refractory to immune checkpoint blockade therapy. KRAS is a gatekeeper gene in colorectal tumorigenesis. Nevertheless, KRAS is ‘undruggable’ due to its structure. Thus, focus has been diverted to develop small molecule inhibitors for its downstream effector such as ERK/MAPK. Despite intense research efforts for the past few decades, no small molecule inhibitor has been in clinical use for CRC. Antibody targeting KRAS itself is an attractive alternative. We developed a transient ex vivo patient-derived matched mucosa-tumor primary culture to assess whether anti-KRAS antibody can be internalized to bind and inactivate KRAS. We showed that anti-KRAS antibody can enter live mucosa-tumor cells and specifically aggregate KRAS in the cytoplasm, thus hindering its translocation to the inner plasma membrane. The mis-localization of KRAS reduces KRAS dwelling time at the site where it tethers to activate downstream effectors. We previously showed that expression of SOX9 was KRAS-mutation-dependent and possibly a better effector than ERK in CRC. Herein, we showed that anti-KRAS antibody treated tumor cells have less intense SOX9 cytoplasmic and nuclear staining compared to untreated cells. Our results demonstrated that internalized anti-KRAS antibody inhibits KRAS function in tumor. With an efficient intracellular antibody delivery system, this can be further developed as combinatorial therapeutics for CRC and other KRAS-driven cancers.

show abstract

Cetuximab therapy in the treatment of metastatic colorectal cancer: The future frontier?

Abstract: The use of cetuximab to conventional chemotherapy regimens may improve the efficacy of down-staging programmes, leading to more patients being offered potentially curative resection.

Cited by 11 publications

References 47 publications

Resection margin influences the outcome of patients with bilobar colorectal liver metastases

Resection margin influences the outcome of patients with bilobar colorectal liver metastases

Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer

KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane

Contact Info

Product

Resources

About