Tomudex (raltitrexed) / Pfizer, AstraZeneca - LARVOL DELTA

Short-course hypofractionated radiotherapy in combination with raltitrexed and tislelizumab in patients with region-relapsed or progressive esophageal squamous cell carcinoma: Medium-term analysis (ESMO Asia 2025) - P | "The SCHRT regimen was effective with acceptable safety in patient with RPESCC."

Clinical • Combination therapy • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Overcoming diagnostic pitfalls in primary gastric squamous cell carcinoma: the imperative of adequate sampling in an elderly female patient, case report. (PubMed, Front Oncol) - "Given the patient's advanced age, poor physical condition, and refusal of surgery, a palliative treatment plan of "Raltitrexed + Sintilimab" was finally decided upon after a multidisciplinary consultation. This case highlights the importance of adequate sampling in the diagnosis of gastric squamous cell carcinoma to avoid misdiagnosis due to limited specimens. It also provides a potential treatment option of immune therapy combined with low-dose chemotherapy for elderly patients with gastric squamous cell carcinoma who are not suitable for surgery."

Journal • Gastric Cancer • Oncology • Pain • Palliative care • Squamous Cell Carcinoma • MUC5AC • TP63

Identifying metabolic vulnerabilities of recurrent IDH1-R132H mutant glioma by high throughput screening (SNO 2025) - "Notable target pathways include folate metabolism and de novo thymidylate synthesis (methotrexate, raltitrexed, 5-FU), p97 AAA ATPase/VCP chaperone (CB-5083, ML240, eeyarestatin I), mevalonate pathway (Ro 48-8071 fumarate, atorvastatin calcium), and the BCL-2 family (Navitoclax, ABT-737). We are validating these drugs across a panel of patient-derived IDH-mutant gliomasphere models, and examining the combinatorial effects of these agents with vorasidenib and CDK4/6 inhibitors. Our results provide insight into important metabolic pathway dependencies in recurrent IDH1-R132H mutant gliomas that have targeting potential."

IO biomarker • Brain Cancer • Glioma • Oligodendroglioma • Solid Tumor • BCL2 • IDH1 • NAMPT

Identifying metabolic vulnerabilities of recurrent IDH1-R132H mutant glioma by high throughput screening (WFNOS 2025) - "Notable target pathways include folate metabolism and de novo thymidylate synthesis (methotrexate, raltitrexed, 5-FU), p97 AAA ATPase/VCP chaperone (CB-5083, ML240, eeyarestatin I), mevalonate pathway (Ro 48-8071 fumarate, atorvastatin calcium), and the BCL-2 family (Navitoclax, ABT-737). We are validating these drugs across a panel of patient-derived IDH-mutant gliomasphere models, and examining the combinatorial effects of these agents with vorasidenib and CDK4/6 inhibitors. Our results provide insight into important metabolic pathway dependencies in recurrent IDH1-R132H mutant gliomas that have targeting potential."

IO biomarker • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • BCL2 • IDH1 • NAMPT

Cerebral Spinal Fluid Attenuates the Efficacy of Methotrexate Against Acute Lymphoblastic Leukemia Cells (ASH 2023) - "While this was confirmed for several ALL drugs including cytarabine and anthracyclines, we strikingly found that methotrexate was significantly less efficacious and potent against ALL cells in CSF relative to standard tissue culture media or the more physiologically relevant human plasma-like media (HPLM). CSF also attenuated the sensitivity of ALL cells to other anti-folates including raltitrexed, trimetrexate, and pralatrexate...Activation of the UPR with thapsigargin, a sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor that triggers ER stress, increased methotrexate resistance in leukemia cells...Moreover, we anticipate that our current work defining the mechanisms driving this resistance may identify novel approaches for maximizing methotrexate efficacy and more completely eradicating leukemia cells in CSF and the CNS. Finally, this work highlights the importance of critically evaluating even long-established standards of care."

Clinical • Acute Lymphocytic Leukemia • Central Nervous System Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Pathways in the brain, heart and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence. (PubMed, Cardiooncology) - "This study highlights probable hub genes, drugs targeting them, and associated pathways perturbed by SARS-CoV-2 NSP6. Galectin3 (LGALS3) upregulated in both heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies for present scenario of long and recurrent COVID-19."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Lung Cancer • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • ATP6AP1 • ATP6V1D • CANX • CCNA1 • CCNB1 • CCND1 • CCNE1 • CDKN1B • EGF • LAMP2 • LGALS3 • TGFB1 • TGFBR2

Study on drug sensitivity and clinical application of tumor organoid-based colorectal cancer models. (PubMed, Am J Transl Res) - "CRC PDOs can be efficiently established and serve as reliable in vitro models for predicting responses to chemotherapy and targeted therapies. This approach may guide personalized treatment strategies and improve clinical decision-making in CRC."

Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor

Rare double primary carcinoma in ileocecal region: cecal tubular adenocarcinoma combined with appendiceal goblet cell adenocarcinoma. (PubMed, Diagn Pathol) - "Appendiceal GCA is more common in middle-aged and elderly women and is associated with a good overall survival rate but a high risk of long-term recurrence and metastasis, especially in patients with distant metastases. The coexistence of appendiceal GCA and cecal tubular adenocarcinoma is exceedingly rare. This case report analyzes the clinical features, histological morphology, immunohistochemistry, and differential diagnosis of this condition to enhance understanding of this rare disease."

Journal • Appendix Cancer • Carcinoid Tumor • Colon Cancer • Colorectal Cancer • Oncology • Pain • Rare Diseases • Solid Tumor

Designing and computational studies of Novel 5-Fluorouracil hybrids as thymidylate synthase inhibitors for targeting non small cell lung cancer. (PubMed, Comput Biol Chem) - "The objectives of our recent study were to design and evaluate 5-FU-based hybrids that can inhibit TS in comparison to already known inhibitors such as Raltitrexed. Docking investigation utilised the crystal structure of the thymidylate synthase inhibitor enzyme (PDB ID: 6ZXO). Further, MD simulations and QSAR Studies were performed, and satisfactory results were obtained, suggesting future potential drugs for the treatment of NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Salvage treatment of a metastatic colorectal cancer with pMMR/MSS in a 21-year-old man: a case report. (PubMed, Front Oncol) - "The fourth-line treatment, including tislelizumab, regorafenib, pemetrexed, and raltitrexed, was administered with a progression-free survival (PFS) of 13 months. Then, this patient received fifth-line treatment with chidamide, fruquintinib, toripalimab, raltitrexed, and nanoparticle albumin-bound paclitaxel with a PFS of 8 months...The sixth-line regimen was started, and he is still under follow-up. Collectively, this patient achieved long-term survival with a high quality of life through therapies beyond the third line."

Journal • pMMR • Bladder Cancer • Colorectal Cancer • Oncology • Solid Tumor

Design, synthesis, and biological evaluation of 6-methylated pyrrolo[3,2-d]pyrimidines as antifolates for selective transport to cancer cells (ACS-Fall 2025) - "Clinically utilized antifolates, including Pemetrexed, Methotrexate, Pralatrexate, and Raltitrexed, are all transported by the ubiquitously expressed reduced folate carrier (RFC; SLC19A1) and the tumor-selective proton-coupled folate transporter (PCFT; SLC46A1). Importantly, inhibition of the principal cellular target (serine hydroxymethyltransferase 2) was preserved, although there were variable losses of de novo purine biosynthesis at glycinamide ribonucleotide formyl transferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase for the 6-methyl and desmethyl compounds. The design, synthesis, crystal structures, and biological activities of the 6-methylated pyrrolo[3,2-d]pyrimidine antifolates will be presented."

Oncology • SHMT2

The Clinical Trial of Tirelizumab, Regorafenib and Raltitrexed for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy (ChiCTR) - P4 | N=38 | Recruiting | Sponsor: Army Medical Center of PLA; Army Medical Center of PLA

New P4 trial • Colorectal Cancer • Oncology • Solid Tumor

Prolonged Progression-Free Survival in a Patient with Highly Pretreated Recurrent Ovarian Cancer after Developing Multisystem Immune-Related Adverse Events: A Case Report and Literature Review. (PubMed, Case Rep Oncol) - "Between 2013 and 2021, she underwent palliative chemotherapy comprising paclitaxel liposomes, cisplatin/nedaplatin, S-1/raltitrexed, irinotecan, doxorubicin, vinorebine, toripalimab, apatinib, gemcitabine, oxaliplatin, and capecitabine, as well as two debulking surgeries. From November 2021, she received six cycles of tislelizumab (a PD-1 inhibitor), paclitaxel (albumin-bound), and carboplatin, to which a partial response was observed according to the Response Evaluation Criteria in Solid Tumors. From May 2022, the patient was switched to maintenance therapy with tislelizumab plus olaparib...We report a case involving a patient with highly pretreated recurrent ovarian cancer who exhibited prolonged PFS after developing three irAEs. The distinctly prolonged PFS observed, along with the reviewed literature, suggests that irAEs may be correlated with improved survival in ovarian cancer."

Adverse events • IO biomarker • Journal • Tumor mutational burden • Endocrine Disorders • Gynecology • Microsatellite Instability • Nephrology • Obstetrics • Oncology • Ovarian Cancer • Pneumonia • Renal Disease • Solid Tumor • MSI • TMB

Raltitrexed as a substitute for 5-fluorouracil in combination with pembrolizumab and platinum in a patient with metastatic esophageal squamous cell carcinoma and coronary artery disease: a case report. (PubMed, Ann Transl Med) - "Considering his significant cardiac history, 5-FU was replaced with raltitrexed and combined with carboplatin and pembrolizumab. In addition to an encouraging progression-free survival (PFS), the patient reported an overall improvement in quality of life while on therapy with no signals of toxicity from raltitrexed or immunotherapy. Overall, the present case demonstrates that chemotherapy in combination with immunotherapy for the treatment of advanced esophageal cancer appears to be safe and effective when raltitrexed is substituted for 5-FU, which is of particular relevance due to the many overlapping characteristics of patients with cardiac pathology and esophageal cancer."

Journal • Acute Coronary Syndrome • Cardiovascular • Coronary Artery Disease • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Disorder • Myocardial Infarction • Oncology • Pain • Squamous Cell Carcinoma

Raltitrexed in HIPEC (clinicaltrials.gov) - P1 | N=27 | Completed | Sponsor: Fudan University | Recruiting ➔ Completed | N=15 ➔ 27 | Trial completion date: Dec 2022 ➔ Apr 2025 | Trial primary completion date: Dec 2021 ➔ Nov 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

Camrelizumab Combined with Lenvatinib and RALOX-Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma (Cal Era): A Prospective, Single-Arm, Phase II Trial. (PubMed, Liver Cancer) - P2 | "This study aimed to assess the efficacy, safety, and potential predictive biomarkers of a therapeutic approach incorporating camrelizumab, lenvatinib, and a HAIC protocol using raltitrexed plus oxaliplatin (RALOX) in patients with intermediate-to-advanced HCC. The triple regimen of camrelizumab, lenvatinib, and RALOX-HAIC exhibited notable antitumor capabilities and acceptable tolerability in patients with advanced HCC. Moreover, baseline levels of IL-2, CXCL13, and CCL19 may function as predictive indicators of the response to this first-line therapeutic strategy."

Journal • P2 data • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CCL19 • CXCL13

Hepatic arterial infusion chemotherapy in patients with unresectble hepatocellular carcinoma: 3-year survival update. (PubMed, Hepat Oncol) - P=N/A | "The 3-year survival update confirmed the antitumor activity and long-term survival benefit of HAIC with oxaliplatin plus raltitrexed in patients with unresectable HCC. www.chictr.org.cn identifier is ChiCTR-OOC-17014182."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

HAIC plus TAE combined with tislelizumab and surufatinib in unresectable intrahepatic cholangiocarcinoma: The REACH-01 trial. (ASCO 2025) - P2 | " Twenty-eight patients with pathologically confirmed iCCA received TAE with undrugged microspheres and hepatic arterial infusion of oxaliplatin (85 mg/m2) and raltitrexed (3 mg/m2) at an interval of at least 3 weeks along with intravenous tislelizumab (200 mg) Q3W and oral surufatinib (150 - 250 mg) once daily. HAIC plus TAE combined with tislelizumab and surufatinib are safe and promising first-line treatment selection for unresectable iCCA."

Anorexia • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Real-world study of anti–PD-1 combined with regorafenib and raltitrexed as third-line therapy in colorectal cancer. (ASCO 2025) - "The combination of anti-PD-1 drugs, regorafenib, and raltitrexed demonstrated promising antitumor efficacy and acceptable safety in patients with metastatic CRC, offering an alternative approach to optimize combination strategies in the management of refractory metastatic colorectal cancer. Clinicopathological characteristics."

Clinical • Real-world • Real-world evidence • Colorectal Cancer • Dermatology • Hypertension • Oncology • Solid Tumor

BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress. (PubMed, Nat Commun) - "Therapy with a BCL-2/BCL-XL inhibitor (navitoclax) in combination with thymidylate synthase inhibitors (raltitrexed or capecitabine) causes marked and prolonged tumor regression in prostate and breast cancer xenograft models. These findings indicate that BCL-XL inhibitors may be effective as single agents in a subset of solid tumors with RB1 loss, and that pharmacological induction of replication stress may be a broadly applicable approach for sensitizing to BCL-XL inhibitors."

IO biomarker • Journal • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BCL2 • BCL2L1 • BIRC5 • CDKN1A • RB1

Combined TSA activated DC-CIK/DCvx-CTL group immunotherapy and chemotherapy and radiotherapy treated an advanced GC patient (IGCC 2025) - "He received a combination treatment of cellular immunotherapy (including TSA-DC-CIK and TSA-DCvx-CTL group) and radiotherapy 50Gy/25times for local radiotherapy, as well as Raltitrexed 3mg/m2 , Sintilimab 200mg, Ramucirumab 500mg d1 iv, q3w. Additionally, cell morphology, growth, and stimuli response of DC and T cells were improved. Conclusion This report demonstrates the effectiveness and safety of TSA-DC-CIK and TSA-DCvx-CTL group immunotherapy combined with chemotherapy and radiotherapy treatment on a patient with advanced GC by modifying patient's immune system function."

Clinical • Metastases • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor

Combined TSA activated DC-CIK/DCvx-CTL group immunotherapy and Chemoradiotherapy treated an advanced gastric cancer patient (IGCC 2025) - "He received a combination treatment of cellular immunotherapy (including TSA-DCCIK and TSA-DCvx-CTL group) and radiotherapy 50Gy/25times for local radiotherapy, as well as Raltitrexed 3mg/m2 , Sintilimab 200mg, Ramucirumab 500mg d1 iv, q3w. Additionally, cell morphology, growth, and stimuli response of DC and T cells were improved. Conclusion This report demonstrates the effectiveness and safety of TSA-DC-CIK and TSA-DCvx-CTL group immunotherapy combined with chemotherapy and radiotherapy treatment on a patient with advanced gastric cancer by modifying patient's immune system function."

Clinical • Metastases • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor

RALOX-HAIC (raltitrexed + oxaliplatin) combined with lenvatinib improves survival and safety in elderly patients with unresectable hepatocellular carcinoma. (PubMed, BMC Cancer) - "This study demonstrates that RALOX-HAIC combined with lenvatinib provides superior survival outcomes and tolerability compared to TACE alone ​in elderly patients (≥ 70 years) with unresectable HCC. This combination therapy may be a feasible and safe option for improving the prognosis of elderly patients with uHCC."

Journal • Retrospective data • Dermatology • Hepatocellular Cancer • Oncology • Pain • Solid Tumor

Radiotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors combined with hepatic arterial infusion chemotherapy of RALOX versus FOLFOX for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score-matching cohort study. (PubMed, Discov Oncol) - "The RALOX-HAIC combined radiotherapy, TKI, and ICI may provide similar survival advantages with fewer treatment-related abdominal pain and fever compared to FOLFOX-HAIC for HCC patients with PVTT. The prealbumin < 170 mg/L before therapy is an independent risk factor for OS."

Checkpoint inhibition • Journal • Hepatocellular Cancer • Oncology • Pain • Solid Tumor • Thrombosis

Prediction of Response to Hepatic Arterial Infusion of Raltitrexed and Oxaliplatin (Ralox-HAIC) combined with lenvatinib and camrelizumab for Unresectable Hepatocellular Carcinoma by Machine Learning Radiomics: A Prospective, Single-arm clinical study (APASL 2025) - "Ralox-HAIC combined with lenvatinib and camrelizumab shows promising efficacy and manageable safety in patients with uHCC. Additionally, a predictive nomogram was developed to forecast the efficacy of this treatment strategy. Table and Figure:Figure 1.The PFS and OS of the training and validation sets Figure 2.The nomogram"

Clinical • Machine learning • Hematological Disorders • Hepatitis B • Hepatocellular Cancer • Infectious Disease • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia