Tomudex (raltitrexed)

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.

P1, N=42, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

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.

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.

P2, N=38, Recruiting, Nanfang Hospital, Southern Medical University

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.

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.

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.

P4, N=38, Recruiting, Army Medical Center of PLA; Army Medical Center of PLA

P1, N=27, Completed, Fudan University | Recruiting --> Completed | N=15 --> 27 | Trial completion date: Dec 2022 --> Apr 2025 | Trial primary completion date: Dec 2021 --> Nov 2024

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.

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.