Clinical management of metastatic colorectal cancer in the era of precision medicine

Abstract

Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second most common cause of cancer deaths. Initial clinical presentation as metastatic CRC (mCRC) occurs in approximately 20% of patients. Moreover, up to 50% of patients with localized disease eventually develop metastases. Appropriate clinical management of these patients is still a challenging medical issue. Major efforts have been made to unveil the molecular landscape of mCRC. This has resulted in the identification of several druggable tumor molecular targets with the aim of developing personalized treatments for each patient. This review summarizes the improvements in the clinical management of patients with mCRC in the emerging era of precision medicine. In fact, molecular stratification, on which the current treatment algorithm for mCRC is based, although it does not completely represent the complexity of this disease, has been the first significant step toward clinically informative genetic profiling for implementing more effective therapeutic approaches. This has resulted in a clinically relevant increase in mCRC disease control and patient survival. The next steps in the clinical management of mCRC will be to integrate the comprehensive knowledge of tumor gene alterations, of tumor and microenvironment gene and protein expression profiling, of host immune competence as well as the application of the resulting dynamic changes to a precision medicine-based continuum of care for each patient. This approach could result in the identification of individual prognostic and predictive parameters, which could help the clinician in choosing the most appropriate therapeutic program(s) throughout the entire disease journey for each patient with mCRC.

CAVE-2 (Cetuximab-AVElumab) mCRC: A Phase II Randomized Clinical Study of the Combination of Avelumab Plus Cetuximab as a Rechallenge Strategy in Pre-Treated RAS/BRAF Wild-Type mCRC Patients

“…The introduction of target therapy and the development of continuum of care strategies profoundly changed the treatment landscape for patients with unresectable mCRC, deviating from accounting only for the sidedness of the primary tumor, performance status, volume of disease, and potential resectability to also include the genetics of the tumor and to support the use of precision oncology for treatment decision (3)(4)(5). Although new therapies to further extend survival and quality of life in patients with mCRC are needed, better selection of patients for available treatment choices is also essential.…”

“…Although the advances in screening and medical treatments have led a trend in reduction of both incidence and mortality, almost 20% of patients present metastases at the time of diagnosis, and approximately 35% of patients will subsequently develop a metastatic disease ( 3 ). Over the last several decades, significant advances have been made in the treatment of metastatic CRC (mCRC), resulting in improvements in survival ( 4 ). The increasing number of effective drugs, together with the improvement of surgical procedures and the availability of different local ablative treatment (LAT), led to a significant increase in overall survival (OS) of mCRC patients, which is now ∼30 months ( 5 ).…”

Six Genes Associated with Lymphatic Metastasis in Colon Adenocarcinoma Linked to Prognostic Value and Tumor Immune Cell Infiltration

“…Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second most common cause of cancer deaths [ 1 , 2 ]. Colon adenocarcinoma (COAD), one of the most common pathological types of CRC, has a high fatality rate worldwide [ 3 ].…”

Bio-Inorganic Layered Double Hydroxide Nanohybrids in Photochemotherapy: A Mini Review

“…Cancer therapies have advanced with the development of novel therapeutic models, such as personalized or precision medicine [ 1 , 2 , 3 , 4 ], but they continue to suffer from a considerable number of limitations. One of the most promising therapies, namely, phototherapy [ 5 , 6 , 7 ], has negligible side effects because of high selectivity and can be used to treat even deep-rooted tumors easily, such as liver tumors [ 8 ].…”