Tomudex (raltitrexed) / Pfizer, AstraZeneca - LARVOL DELTA

Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential. (PubMed, Life Sci Alliance) - "Previously, we established that treating HCT116 colon cancer cell lines with either raltitrexed (RTX) or 5-fluoro-2'-deoxyuridine (5FdUR), two potent inhibitors of thymidylate synthase, results in characteristic genomic uracil patterns...The mutational spectra and the clustered nature of these transitions suggested the involvement of APOBEC3 DNA cytidine deaminases, several of which were induced under these conditions. Notably, this mutagenic response coincides with decreased cytotoxicity compared with the low-dose 5FdUR or any efficient doses of RTX, providing insights that may be relevant for personalized cancer therapy."

Journal • Colon Cancer • Oncology • Solid Tumor • TYMS

Chromobox2 inhibition: a novel activity of alisertib, an aurora A kinase inhibitor. (PubMed, Mol Cancer Ther) - "In vitro validation narrowed compounds of interest to raltitrexed, alisertib, GTX-007, LY315920, and PD0325901. Treatment with alisertib leads to decrease in H2AK119ub and shift in the immune tumor microenvironment. Alisertib efficacy in HGSC is dependent on functional CBX2 and cell target engagement confirms selectivity for CBX2, supporting that alisertib activity involves CBX2 inhibition."

Journal • Oncology • AURKA • CBX2

A Prospective, Safety, and Efficacy Clinical Trial of Pressurized Intraperitoneal Aerosol Therapy for Peritoneal Metastasis of Colorectal Cancer (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor

Design, Synthesis, and Anticancer Assessment of Benzylated Pyrrole-Based Pyrido[2,3-d]Pyrimidines as Thymidylate Synthase Inhibitors. (PubMed, Chem Biol Drug Des) - "Compounds 1c and 2i exhibited potent TS inhibition with IC50 values of 11.50 ± 1.08 nM and 17.12 ± 0.91 nM, respectively, comparable to the standard drug raltitrexed (IC50 = 12.51 ± 0.91 nM)...Additionally, compounds 1c and 2i exhibited good stability in 300 ns molecular dynamics simulations along with acceptable drug-like properties and oral bioavailability. These findings suggest that compounds 1c and 2i are promising lead candidates for the development of TS inhibitors."

Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TYMS

The BEVATOMOX phase II trial: raltitrexed/oxaliplatin/bevacizumab vs mFOLFOX6/bevacizumab in 2nd-line metastatic colorectal cancer. (PubMed, Oncologist) - P2 | "The TOMOX-Bev combination is a feasible second-line mCRC treatment with an acceptable toxicity profile. Recruitment failure prevents efficacy conclusions, but TOMOX-Bev may be an alternative if fluropyrimidines are contraindicated."

Journal • P2 data • Colorectal Cancer • Dermatology • Febrile Neutropenia • Hematological Disorders • Mucositis • Neutropenia • Oncology • Solid Tumor • KRAS

QL1706 in Combination With Bevacizumab and RALOX HAIC for Hepatocellular Carcinoma With Vp3/4 PVTT (clinicaltrials.gov) - P2 | N=38 | Recruiting | Sponsor: Nanfang Hospital, Southern Medical University

New P2 trial • Cardiovascular • Hematological Disorders • Hepatocellular Cancer • Oncology • Solid Tumor • Thrombosis

Long-term survival of an advanced gastric cancer patient with multiple liver metastases following maintenance therapy with envafolimab and oral chemotherapy: a case report. (PubMed, Front Oncol) - "The patient had 46 months of overall survival time with a good performance status. This case recommends that maintenance therapy comprising of both PD-L1 blockage and oral fluoropyrimidine can serve as long-duration disease control and significant long-term advantage to a subset of the patients with metastatic immune-cold gastric cancer."

IO biomarker • Journal • Tumor mutational burden • Gastric Adenocarcinoma • Gastric Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • HER-2 • TMB

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