Diagnosis and Treatment of Metastatic Colorectal Cancer

Abstract

ImportanceColorectal cancer (CRC) is the third most common cause of cancer mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal cancer diagnoses, 20% of patients have metastatic disease at presentation and another 25% who present with localized disease will later develop metastases.ObservationsColorectal cancer is the third most common cause of cancer mortality for men and women in the United States, with 53 200 deaths projected in 2020. Among people diagnosed with metastatic colorectal cancer, approximately 70% to 75% of patients survive beyond 1 year, 30% to 35% beyond 3 years, and fewer than 20% beyond 5 years from diagnosis. The primary treatment for unresectable metastatic CRC is systemic therapy (cytotoxic chemotherapy, biologic therapy such as antibodies to cellular growth factors, immunotherapy, and their combinations.) Clinical trials completed in the past 5 years have demonstrated that tailoring treatment to the molecular and pathologic features of the tumor improves overall survival. Genomic profiling to detect somatic variants is important because it identifies the treatments that may be effective. For the 50% of patients with metastatic CRC with KRAS/NRAS/BRAF wild-type tumors, cetuximab and panitumumab (monoclonal antibodies to the epithelial growth factor receptor [EGFR]), in combination with chemotherapy, can extend median survival by 2 to 4 months compared with chemotherapy alone. However, for the 35% to 40% of patients with KRAS or NRAS sequence variations (formerly termed mutations), effective targeted therapies are not yet available. For the 5% to 10% with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors extended overall survival to 9.3 months, compared to 5.9 months for those receiving standard chemotherapy. For the 5% with microsatellite instability (the presence of numerous insertions or deletions at repetitive DNA units) or mismatch repair deficiency, immunotherapy may be used in the first or subsequent line and has improved treatment outcomes with a median overall survival of 31.4 months in previously treated patients.Conclusions and RelevanceAdvances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.

Mesenchymal Stem Cell-Based Therapy For Advanced Colorectal Cancer: Potential Mechanisms Of Therapy And Associated Risks

“…With our current understanding of colorectal cancer stem cells, it is clear that conventional methods of treatment only induce partial or incomplete remission. Surgical excision of localized disease is currently the only effective management strategy being employed against this heterogeneous population of cells [2]. Therefore, there is an urgent need to develop novel therapies that can target this unique population of CCSCs [1][2][3][4][5].…”

“…Surgical excision of localized disease is currently the only effective management strategy being employed against this heterogeneous population of cells [2]. Therefore, there is an urgent need to develop novel therapies that can target this unique population of CCSCs [1][2][3][4][5]. In order to design completely effective treatment strategies to fight colon cancer, it is imperative to understand the biology of CCSCs and their interactions with the TME.…”

“…Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for nearly two million cases in 2020 with approximately 50% mortality [1][2]. Also referred to as colorectal adenocarcinoma, CRC typically emerges from the glandular epithelial cells of the large intestine [2]. Colorectal carcinogenesis is driven by the sequential acquisition of genetic and epigenetic alterations during which normal colonic epithelium is converted into metastatic carcinoma.…”

Selective in vitro cytotoxicity effect of Drimia calcarata bulb extracts against p53 mutant HT-29 and p53 wild-type Caco-2 colorectal cancer cells through STAT5B regulation

“…The prime treatment for unresectable metastatic colorectal cancer is a systemic therapy. Clinical trials done in the previous five years have proved that modifying treatment to the molecular and pathologic features of the tumour enhances overall survival [ 14 ], even though the clinical outcomes and treatment responses of each patient with colorectal cancer differ greatly [ 15 ], the use of standardized treatment possibilities is limited in standard practice [ 16 , 17 ]. As a component of first- and second-line combination therapies, oxaliplatin is used to treat metastatic colorectal cancer.…”

Surgical treatment strategy for locally advanced colorectal cancer with abdominal wall invasion

“…If after treatment, the conditions for surgery are met and surgical treatment is possible. If there is no surgery conditions, local or systemic drug treatment is given (15). There are two basic categories of surgery, radical resection and palliative resection.…”