Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates of CIT. This complication often leads to treatment delays, dose reductions, and elevated bleeding risk. This review provides a comprehensive overview of the pathophysiology, clinical implications, and management strategies of CIT in GI malignancies. CIT arises from several mechanisms: direct cytotoxicity to megakaryocyte progenitors, disruption of the marrow microenvironment, thrombopoietin dysregulation, and immune-mediated platelet destruction. Platinum agents, antimetabolites, and immune checkpoint inhibitors can contribute to these effects. Oxaliplatin-induced CIT may occur acutely via immune mechanisms or chronically through marrow suppression. CIT affects 20–25% of solid tumor patients, with highest rates in those receiving gemcitabine (64%), carboplatin (58%), and oxaliplatin (50%). Within GI cancer regimens, FOLFOXIRI and S-1 plus oxaliplatin show higher CIT incidence compared to FOLFIRI and CAPIRI. Thrombocytopenia is graded by severity, from mild (Grade 1–2) to severe (Grade 3–4), and often necessitates treatment adjustments, transfusions, or supportive therapies. Current strategies include chemotherapy dose modification, platelet transfusion, and thrombopoietin receptor agonists (TPO-RAs) like romiplostim and eltrombopag. While platelet transfusions help in acute settings, TPO-RAs may preserve dose intensity and reduce bleeding. Emerging agents targeting megakaryopoiesis and marrow protection offer promising avenues for long-term management.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059–0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavi-ly-glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of IM and MM isoforms of MUC5AC using respective monoclonal antibodies CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular, EC) was determined, and H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (N=100), IM expression (objective response vs. no response vs. UpS = H-scores 104 vs. 152 vs. 163, p=0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p=0.02) were significantly different. In the NAT-group, MM-MUC5AC-negative patients had significantly better PFS on MVA (Hazard Ratio, 0.2, 95 % CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (N=36). We established an association of MUC5AC expression with treatment response and outcomes.

Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates of CIT. This complication often leads to treatment delays, dose reductions, and elevated bleeding risk. This review provides a comprehensive overview of the pathophysiology, clinical implications, and management strategies of CIT in GI malignancies.CIT arises from several mechanisms: direct cytotoxicity to megakaryocyte progenitors, disruption of the marrow microenvironment, thrombopoietin dysregulation, and immune-mediated platelet destruction. Platinum agents, antimetabolites, and immune checkpoint inhibitors can contribute to these effects. Oxaliplatin-induced CIT may occur acutely via immune mechanisms or chronically through marrow suppression. CIT affects 20–25% of solid tumor patients, with highest rates in those receiving gemcitabine (64%), carboplatin (58%), and oxaliplatin (50%). Within GI cancer regimens, FOLFOXIRI and S-1 plus oxaliplatin show higher CIT incidence compared to FOLFIRI and CAPIRI.Thrombocytopenia is graded by severity, from mild (Grade 1-2) to severe (Grade 3-4), and often necessitates treatment adjustments, transfusions, or supportive therapies. Current strategies include chemotherapy dose modification, platelet transfusion, and thrombopoietin receptor agonists (TPO-RAs) like romiplostim and eltrombopag. While platelet transfusions help in acute settings, TPO-RAs may preserve dose intensity and reduce bleeding. Emerging agents targeting megakaryopoiesis and marrow protection offer promising avenues for long-term management.

Background: We explored the potential value of serum MUC5AC (sMUC5AC) as a biomarker to guide perioperative management of early-stage pancreatic ductal adenocarcinoma (PDA) patients receiving neoadjuvant therapy (NAT). Methods: We performed enzyme-linked immunoassays using a human MUC5AC kit (NBP2-76703) in serum samples obtained from The Ohio State University biorepository (between January 2010 and June 2021). Univariate (UV) and multivariate (MV) Cox regression models were used to quantify progression-free survival (PFS); clinical and pathological variables were adjusted in the MV models. UV logistic regression analysis was utilized to examine the association of sMUC5AC with pathological features and survival. 2 Results: Overall, 23 samples (19 FOLFIRINOX, 3 gemcitabine/nab-paclitaxel, 1 FOLFOX) were available for analysis. The median age was 66 years, and 52% were females. sMUC5AC was associated with a) treatment response, margin status, and residual disease (R0 vs. R1/R2) (all P<0.05); b) PFS on both UV (hazard ratio (HR) of 1.4, 95% confidence interval (CI) of 1.07 to 1.82, P=0.01) and MV (HR of 49.2, 95% CI, 4.4 to 1008.3, P=0.002) analyses; and c) PFS in pre-surgery models along with carbohydrate antigen 19-9 (CA19-9) measured on the same day alone (HR of 1.47, 95% CI, 1.06 to 1.93, p=0.04), with CA19-9 on the same day, and NAT regimen (HR of 1.44, 95% CI, 1.12 to 1.93, p=0.01), and with CA19-9 on the same day, NAT regimen, and CA19-9 at diagnosis (HR of 1.52, 95% CI, 1.1 to 2.09, p=0.007). Conclusion: sMUC5AC shows promise to helping to predict outcomes in our preliminary study. Larger prospective studies should validate these findings.