The Molecular Mechanism of RAS Wild-type mCRC Resistance to Anti-EGFR-antibody

The Molecular Mechanism of RAS Wild-type Metastatic Colorectal Cancer (mCRC) Resistance to Anti Epidermal Growth Factor Receptor (EGFR) Antibody

Establishing the genetic map of primary and secondary resistance of Chinese wild RAS colorectal cancer received anti-EGFR treatment through tissues and peripheral blood NGS testing. Combination genetic data with clinical characteristics, prognosis and treatment data to explore the molecular mechanism of resistance of anti-EGFR-antibody.

Cetuximab is a chimeric (mouse/human) monoclonal antibody, an epidermal growth factor receptor (EGFR) inhibitor. Many large clinical trials demonstrated that for RAS wild-type metastatic colorectal cancer (mCRC), especially left-sided RAS wild-type mCRC, cetuximab can prolong OS. But some of patients have primary resistance to cetuximab and for all patients received cetuximab will develop secondary resistance. Cell-free or circulating tumour DNA (ctDNA) including primary site and metastatic site genetic information, which can avoid tumor heterogeneity. The results of paired test detection of tissue and ctDNA showed there is 93% consistency in RAS testing. Therefore, dynamic monitoring ctDNA during anti-EGFR targeted treatment of RAS wild-type mCRC patients can implement prognosis of efficacy and response evaluation in real-time. Besides, it can monitor the variation features of resistance gene and find resistance gene in real-time. According the situation of gene change to find potential drug resistance mechanism and formulate individualization treatment plan.

Inclusion Criteria:

1. Age≥18 years, ≤75 years, all gender;
2. Histologically proven metastatic adenocarcinoma of colorectal cancer, no previous history of cancer;
3. The clinical data of patient is intact;
4. The data of patients after surgery is intact, and the prognosis follow-up data of patient is available.

Exclusion Criteria:

1. Previous history of cancer；
2. Intact clinical data or diagnosis results of histopathology is unavailable;
3. Time of progression disease after treatment and follow-up data are unavailable;
4. Patient received blood transfusion within 3 months;
5. Other situation that researchers think it will impact the results of trails or violate ethics.