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Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer.

ABSTRACT: BACKGROUND:Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. METHODS:A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. RESULTS:RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-?, which require further research. CONCLUSION:Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients.

SUBMITTER: Lai E

PROVIDER: S-EPMC7281737 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer.

Lai Eleonora E Liscia Nicole N Donisi Clelia C Mariani Stefano S Tolu Simona S Pretta Andrea A Persano Mara M Pinna Giovanna G Balconi Francesca F Pireddu Annagrazia A Impera Valentino V Dubois Marco M Migliari Marco M Spanu Dario D Saba Giorgio G Camera Silvia S Musio Francesca F Ziranu Pina P Puzzoni Marco M Demurtas Laura L Pusceddu Valeria V Dettori Manuela M Massa Elena E Atzori Francesco F Dessì Mariele M Astara Giorgio G Madeddu Clelia C Scartozzi Mario M

Cancers 20200513 5

<h4>Background</h4>Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients.<h4>Methods</h4>A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications.<h4>Results</h4><i>RAS</i> wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge str ...[more]

PMID: 32413973

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Project description:PurposeTo develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC).MethodsASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.ResultsFive systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria.RecommendationsDoublet chemotherapy should be offered, or triplet therapy may be offered to patients with previously untreated, initially unresectable mCRC, on the basis of included studies of chemotherapy in combination with anti-vascular endothelial growth factor antibodies. In the first-line setting, pembrolizumab is recommended for patients with mCRC and microsatellite instability-high or deficient mismatch repair tumors; chemotherapy and anti-epidermal growth factor receptor therapy is recommended for microsatellite stable or proficient mismatch repair left-sided treatment-naive RAS wild-type mCRC; chemotherapy and anti-vascular endothelial growth factor therapy is recommended for microsatellite stable or proficient mismatch repair RAS wild-type right-sided mCRC. Encorafenib plus cetuximab is recommended for patients with previously treated BRAF V600E-mutant mCRC that has progressed after at least one previous line of therapy. Cytoreductive surgery plus systemic chemotherapy may be recommended for selected patients with colorectal peritoneal metastases; however, the addition of hyperthermic intraperitoneal chemotherapy is not recommended. Stereotactic body radiation therapy may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection. Selective internal radiation therapy is not routinely recommended for patients with unilobar or bilobar metastases of the liver. Perioperative chemotherapy or surgery alone should be offered to patients with mCRC who are candidates for potentially curative resection of liver metastases. Multidisciplinary team management and shared decision making are recommended. Qualifying statements with further details related to implementation of guideline recommendations are also included.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Dataset Information

Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer.

Publications

Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer.

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