Colon cancer is a leading cause of cancer-related mortality worldwide, with surgical resection followed by adjuvant chemotherapy being the traditional standard for localized disease. However, the emergence of neoadjuvant therapies has introduced new possibilities for improving outcomes in locally advanced colon cancer (LACC). Neoadjuvant chemotherapy has demonstrated promising results in tumor downstaging, improved resectability, and reduced recurrence rates, as highlighted in trials like FOxTROT (Fluoropyrimidine oxaliplatin and targeted receptor pre-operative therapy), OPTICAL (A phase III study to evaluate the 3-year disease-free survival in patients with locally advanced colon cancer receiving either perioperative or postoperative chemotherapy with FOLFOX or CAPOX regimens), and NeoCol (Neoadjuvant chemotherapy versus standard treatment in patients with locally advanced colon cancer). For deficient mismatch repair (dMMR) tumors, neoadjuvant immunotherapy, exemplified by the NICHE (Neoadjuvant immune checkpoint inhibition and novel IO combinations in early-stage colon cancer) trial, has shown good pathologic response rates. Despite these advancements, challenges such as disease progression during treatment, staging inaccuracies, and chemotherapy-related toxicities underscore the need for precise patient selection and monitoring. Immunotherapy offers significant potential for dMMR tumors, potentially leading to non-surgical management strategies, while neoadjuvant chemotherapy presents a viable option for MMR-proficient (pMMR) patients, improving long-term outcomes in select populations. As the landscape of LACC management evolves, this review emphasizes the importance of personalized treatment strategies informed by biomarkers such as MMR status to maximize therapeutic efficacy and minimize risks. Future directions include refining the role of neoadjuvant therapies in clinical practice, expanding the use of immunotherapy, and exploring innovative combinations of systemic and targeted approaches to enhance survival and quality of life in patients with LACC. This review examines the current evidence supporting neoadjuvant approaches in pMMR and dMMR colon cancer, emphasizing their potential benefits and challenges.
Humans ; Neoadjuvant Therapy/methods* ; Colonic Neoplasms/therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immunotherapy/methods* ; Chemotherapy, Adjuvant

A general effect for cell proliferation has been incorporated into Roesch's survival equation(Accumulation Model). From this an isoeffect formula for the low dose-rate regimen is obtained. The prediction for total doses equivalent to 60 Gy delivered at the constant dose-rate over 7 days agrees well with the dose-time data of Paterson and of Green, when the parameter ratio A/B(»am/2betahere m is the repair rate) is chosen to be 0.7 Gy/h. When a constant proliferation rate and known facts of division delay are assumed, an isoeffect relation between low dose-rate treatment and acute dose-rate treatment can be derived. This formula in the regimens where proliferation is negligible predicts exactly the data of Ellis that 8 fractions of 5 Gy/day for 7 days are equivalent to continuously applied 60 Gy over 7 days, provided the A/B ratio is 0.7 Gy/h and the a/b ratio is 4 Gy. Overall agreement between the clinical data and the predictions made by the formula at the above parameter values suggests that the biological end points used as the tolerance level in the studies by Paterson, Green, and Ellis all agree and they are not entirely the early effects as generally assumed. The absence of dose-rate effects observed in the mouse KHT sarcoma can bettor be explained in terms of a large value for the A/B ratio. Similarly, the same total dose used independently of the dose-rate to treat head and neck tumors by Pierquin can be justified.
Animals ; Cell Proliferation ; Cell Survival ; Head ; Mice ; Neck ; Regeneration* ; Sarcoma