Fanconi Anemia Pathway in Colorectal Cancer: A Novel Opportunity for Diagnosis, Prognosis and Therapy

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and has the second highest mortality rate globally. Thanks to the advent of next-generation sequencing technologies, several novel candidate genes have been proposed for CRC susceptibility. Germline biallelic mutations in one or more of the 22 currently recognized Fanconi anemia (FA) genes have been associated with Fanconi anemia disease, while germline monoallelic mutations, somatic mutations, or the promoter hypermethylation of some FANC genes increases the risk of cancer development, including CRC. The FA pathway is a substantial part of the DNA damage response system that participates in the repair of DNA inter-strand crosslinks through homologous recombination (HR) and protects genome stability via replication fork stabilization, respectively. Recent studies revealed associations between FA gene/protein tumor expression levels (i.e., FANC genes) and CRC progression and drug resistance. Moreover, the FA pathway represents a potential target in the CRC treatment. In fact, FANC gene characteristics may contribute to chemosensitize tumor cells to DNA crosslinking agents such as oxaliplatin and cisplatin besides exploiting the synthetic lethal approach for selective targeting of tumor cells. Hence, this review summarizes the current knowledge on the function of the FA pathway in DNA repair and genomic integrity with a focus on the FANC genes as potential predisposition factors to CRC. We then introduce recent literature that highlights the importance of FANC genes in CRC as promising prognostic and predictive biomarkers for disease management and treatment. Finally, we represent a brief overview of the current knowledge around the FANC genes as synthetic lethal therapeutic targets for precision cancer medicine.

Risk factors for sepsis in patients with colorectal cancer complicated with gastrointestinal perforation and its impact on prognosis

“…Digestive tract tumors can cause anemia in several ways: (I) Secretion of cytokines inhibits hematopoietic function; (II) digestive tract tumors lead to malnutrition, resulting in a serious lack of vitamins, iron, folic acid, and other hematopoietic raw materials; and (III) trans-gastrointestinal bleeding. Therefore, it is more common for colorectal cancer patients to have anemia, especially in patients with colorectal cancer in the middle and advanced stages ( 9 - 12 ). Patients with anemia have decreased immune function and are prone to sepsis ( 13 - 15 ).…”

IL22RA1/JAK/STAT Signaling Acts As a Cancer Target Through Pan-Cancer Analysis

“…IL22RA1 mutation in uterine cancer upregulated genes in the fanconi anemia pathway and homologous recombination which were involved in DNA damage and repair. Upregulation of the fanconi anemia pathway components such as RAD51 and BRCA1/2, leads to homologous recombination restoration and drug resistance (34,35).…”

Inflammasomes Are Influenced by Epigenetic and Autophagy Mechanisms in Colorectal Cancer Signaling

“…Recently, mutations in FANC genes, including FANCC, have been identified in CRC patients who did not have mutations in established CRC susceptibility genes. This discovery emphasizes the possible involvement of FANC genes as predisposition genes in sporadic CRC [ 102 , 103 ]. The interaction between FANCC and Parkin promotes mitophagy, a process which suppresses inflammasome activation [ 104 ].…”