DeCure for Colon carcinoma

Colorectal cancer arises through the progressive accumulation of genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinoma, a process that unfolds over 10–15 years and proceeds through parallel histologic and molecular changes. Three central tenets emerge from this analysis: cancer emerges via multi-step progression at both molecular and morphologic levels, loss of genomic stability is a key molecular step in cancer formation, and hereditary cancer syndromes frequently correspond to germline forms of key genetic defects whose somatic occurrences drive sporadic colon cancers. Specific pathogenetic mechanisms include tumour cell cohesiveness mediated by adhesion proteins, mutations and loss of heterozygosity of tumour suppressor genes such as the adenomatous polyposis coli gene, and germline mutations in mismatch repair genes causing generalised genetic instability as seen in hereditary nonpolyposis colorectal cancer.

By 2020, approximately 1,900,000 cases of colorectal cancer were detected worldwide, and the American Cancer Society identified 104,610 new cases in the United States with 53,200 deaths. The disease is a genetically inherited multifactorial condition in which genetic, immunologic and environmental factors all play significant roles in development and metastasis. Carcinogenesis involves staged interactions of suppressor genes and oncogenes, including p53, APC and KRAS, and family history of adenomatous polyposis confers high risk. Current treatment is based on radical surgery combined with systemic or local radiotherapy and chemotherapy, and although combined therapy has dramatically improved survival rates and life quality, a large percentage of patients still die of recurrence and metastasis.

For obstructed colon cancer, the key priority is urgent resolution of large bowel obstruction with ideally no compromise of oncological outcomes and low initial and permanent ostomy rates. Proactive management is pivotal to decrease the risk of perforation and septic shock, and staged procedures have an important place, offering similar treatment and outcomes as in the elective setting. The approach is tailored to the patient's condition, oncological situation and expertise of the available surgical team. New targeted drugs and chemotherapeutic drugs have led to significantly improved therapeutic efficacy and better life quality, but how to choose and use these treatments synthetically and reasonably remains a challenge to surgeons.

The foundations of the drug discovery process need reconsideration, with more emphasis on the quality of preclinical validations and the design of pertinent models, including human three-dimensional in vitro cell models and tissue explants. Current models used to study colorectal cancer include cancer cell line collections, genetically engineered mouse models, primary human tumour xenografts and ex vivo organotypic cultures. Gene therapy approaches have reached clinical testing stages, but the safety of such treatment remains a hot topic. What is still missing is robust validation of these preclinical biosystems against clinical outcomes, prospective data on how molecular stratification of patients by APC, p53 and KRAS status alters treatment response, and trial designs that address recurrence and metastasis rather than only initial tumour shrinkage.