Fanelli Giuseppe Nicolò, Dal Pozzo Carlo Alberto, Depetris Ilaria, Schirripa Marta, Brignola Stefano, Biason Paola, Balistreri Mariangela, Dal Santo Luca, Lonardi Sara, Munari Giada, Loupakis Fotios, Fassan Matteo
1Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, via Gabelli 61, 35121 Padua, Italy.
2Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Cancer Cell Int. 2020 Jan 29;20:30. doi: 10.1186/s12935-020-1117-2. eCollection 2020.
Colorectal cancer (CRC) is a complex and molecularly heterogeneous disease representing one of the most frequent causes of cancer-related death worldwide. About 8-15% of CRCs harbor a mutation in gene, a proto-oncogene involved in cell proliferation, differentiation and survival through the MAPK signaling cascade. The acquisition of mutation is an early event in the "serrated" CRC carcinogenetic pathway and is associated with specific and aggressive clinico-pathological and molecular features. Despite that the presence of mutation is a well-recognized negative prognostic biomarker in metastatic CRC (mCRC), a great heterogeneity in survival outcome characterizes these patients, due to the complex, and still not completely fully elucidated, interactions between the clinical, genetic and epigenetic landscape of mutations. Because of the great aggressiveness of -mutated mCRCs, only 60% of patients can receive a second-line chemotherapy; so intensive combined and tailored first-line approach could be a potentially effective strategy, but to minimize the selective pressure of resistant clones and to reduce side effects, a better stratification of patients bearing mutations is needed.
结直肠癌（CRC）是一种复杂的分子异质性疾病，是全球癌症相关死亡的最常见原因之一。约8%-15%的结直肠癌患者携带 基因的突变，该原癌基因通过丝裂原活化蛋白激酶（MAPK）信号级联参与细胞增殖、分化和存活。 突变的获得是“锯齿状”结直肠癌致癌途径中的早期事件，并且与特定的侵袭性临床病理和分子特征相关。尽管 突变的存在是转移性结直肠癌（mCRC）中公认的不良预后生物标志物，但由于 突变的临床、遗传和表观遗传格局之间复杂且仍未完全阐明的相互作用，这些患者的生存结果存在很大的异质性。由于携带 突变的mCRC具有很强的侵袭性，只有60%的患者能够接受二线化疗；因此，强化联合和个体化的一线治疗方法可能是一种潜在有效的策略，但为了最小化耐药克隆的选择压力并减少副作用，需要对携带 突变的患者进行更好的分层。
