Colorectal Cancer: Personalized Therapy

Abstract

Background: Colorectal cancer (CRC) is the second most common type of cancer in the Western world. The treatment of this disease has evolved greatly, particularly for patients with metastatic disease. The advent of combination chemotherapy plus targeted agents has led to more curative resections and improved survival rates in these patients. A deeper understanding of the mechanisms of tumorigenesis has facilitated tumor characterization, prognosis and patient stratification, bringing us one step closer towards personalized medicine. Summary: There are two main pathways of CRC development: (1) chromosomal instability, also known as the classical adenoma-carcinoma sequence, and (2) microsatellite instability, caused by a defective mismatch repair (dMMR) system. Analysis of these pathways has uncovered key prognostic and predictive biomarkers to guide patient selection and treatment strategy. This review summarizes the current treatment regimens and recent advances in the personalized therapy of CRC. Key Message: Understanding of the mechanisms of CRC pathogenesis has led to new developments in tumor characterization, patient stratification, prognosis and treatment, bringing us closer to personalized therapy. Practical Implications: In the adjuvant setting, the treatment decision is driven by clinical and histopathological factors. dMMR status is one of the most robust positive prognostic factors in resected colon cancer. More and more guidelines recommend refraining from adjuvant chemotherapy in patients with dMMR. In the metastatic setting, the introduction of effective compounds, including agents that target the epidermal growth factor receptor and vascular endothelial growth factor pathways, has significantly improved survival. The presence of wild-type KRAS and NRAS (all RAS) is a positive predictive factor for epidermal growth factor receptor antibody treatment. Therefore, analysis of all RAS status is recommended for all patients with metastatic disease prior to the initiation of first-line chemotherapy.

c-MYC Expression Is a Possible Keystone in the Colorectal Cancer Resistance to EGFR Inhibitors

“…The treatment of metastatic colorectal cancer (mCRC) was deeply changed by the introduction of anti-EGFR "targeted therapy" (TT) [1,2]. However, the EGFR blockage therapy is restricted to about 40% mCRC patients not showing KRAS and NRAS oncogenic mutations, the main TT primary molecular resistance, and only half of these are responsive to the TT treatment [3,4].…”

Impact of histological subtype on the prognosis of patients undergoing surgery for colon cancer

“…Even though surgical resection is the only potentially curative therapy for CC, the factors associated with patient prognosis have not been completely understood . In particular, while several clinicopathological variables including advanced AJCC TNM stage, poor differentiated tumor grade, high carcinoembryonic antigen (CEA) level, and lympho‐vascular invasion have been associated with poor prognosis, the role of histology on prognosis is still debated . In fact, even though the majority (80‐90%) of patients with CC has classic adenocarcinoma (CA), 10‐20% of patients has less frequent histological subtypes including mucinous adenocarcinomas (MUC) and signet‐ring cell adenocarcinoma (SC) that have been associated with distinct clinicopathological characteristics and prognosis compared with CA .…”

Pien Tze Huang inhibits the proliferation of colorectal cancer cells by increasing the expression of miR-34c-5p

“…Current therapies for CRC include surgery, radiotherapy and chemotherapy (10,11); however, these treatments have limited efficacy and toxic effects. Therefore, research in this field has been focused on investigating natural products to treat CRC, including traditional Chinese medicine (TCM), as they typically exert fewer side effects than modern medicine (12,13).…”