New Trends in the Therapeutic Approach to Metastatic Colorectal Cancer

Abstract

Important developments in chemotherapy for metastatic colorectal cancer over the last years are reviewed, with an emphasis on the most recently published data from clinical trials. The systematic review of current literature was conducted involving Pubmed Central® research and full articles were obtained and analyzed when appropriate.Fluorouracil still constitutes the backbone of metastatic colorectal cancer treatment; fluorouracil combination plus either irinotecan (FOLFIRI), oxaliplatin (FOLFOX) or capecitabine (CAPOX or XELOX) are chemotherapy protocols established as treatments producing similar outcomes.Actual treatment involves these chemotherapy protocols in combination with new molecular targeted drugs: bevacizumab and aflibercept (anti-vascular endothelial growth factor monoclonal antibody) and cetuximab and panitumumab (anti-epidermal growth factor receptor monoclonal antibody for patients with wild type KRAS) which confer significant survival benefits in select patients as first- or second-line therapies. The factors affecting the decisions for one treatment over other are related to the patient and toxicity drug.Finally, metastatic colorectal cancer patients progressing after all standard therapies (maintaining a good ECOG performance status) could be candidates for further therapies such as regorafenib and TAS-102.Regarding the future, promising therapies are under development for the metastatic colorectal cancer treatment and several agents are currently being evaluated in different clinical trials.

Comprehensive review of targeted therapy for colorectal cancer

“…4 However, despite the emergence of numerous screening programs to reduce CRC incidence, nearly a quarter of CRCs are diagnosed at an advanced stage with metastases, and 20% of the remaining cases may develop metachronous metastases, which result in difficulties in curative surgical control and subsequent tumorrelated deaths. [5][6][7][8] For those patients with unresectable lesions or who are intolerant to surgery, the goal is maximum shrinkage of the tumor and suppression of further tumor spread and growth, and radiotherapy and chemotherapy are the leading strategies for controlling disease in such patients. Of note, in some cases, chemotherapy or radiotherapy might be applied before or after surgery as neoadjuvant or adjuvant treatment to maximally reduce and stabilize the tumor.…”

Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening

“…In this context, it is important to know that patients with high-risk stage II and stage III colon cancer are randomly assigned to receive an adjuvant treatment in order to reduce recurrence and metastasis formation [5]. The known drug combinations in CRC treatment are FOLFIRI (leucovorin + 5-fluorouracil (5FU) + irinotecan), and FOLFOX (leucovorin + 5FU + oxaliplatin) that has been shown to improve overall survival by more than 20% compare to surgery alone and is considered a standard treatment [6][7][8]. However, the vast majority of patients will not benefit from receiving adjuvant chemotherapy because they have already been healed by surgery or because of the development of drug resistance [9].…”

Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling

“…panitumumab and cetuximab, in addition to anti-vascular endothelial growth factor (VEGF) agents, e.g. bevacizumab and aflibercept [5][6][7]. As chemotherapy induces toxic effects and targeted therapy is very expensive, thus it is necessary to develop novel therapeutic drugs that might eliminate advanced colorectal adenocarcinoma and mCRC cells [8,9].…”