Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.

Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations.

Considered as a whole, the aqueous leaf extract of Brillantaisia patula reversed oxidative stress and inflammatory side effects of cyclophosphamide, preserving ovarian function and fertility in the rats. This may suggest its exploration as a safe agent against toxic side effects of chemotherapy and fertility-related disorders of the uterus and ovary.

Low‒dose Cy enhances tumoricidal effects of 5‒day spacing high‒dose RT by increasing anti-tumor immune responses.

P=N/A, N=50, Completed, University of Auckland | Recruiting --> Completed

P2, N=32, Enrolling by invitation, The First Affiliated Hospital of Xiamen University

P2, N=36, Not yet recruiting, Washington University School of Medicine

P2, N=30, Not yet recruiting, Fondazione EMN Italy Onlus

P=N/A, N=54, Not yet recruiting, Huashan Hospital, Fudan University; Huashan Hospital, Fudan University

P=N/A, N=30, Not yet recruiting, The Seventh Affiliated Hospital Sun Yat-sen University; The?Seventh?Affiliated?Hospital?Sun?Yat-sen?University

P=N/A, N=50, Not yet recruiting, Beijing Friendship Hospital Pinggu Campus,Capital Medical University; Beijing Friendship Hospital Pinggu Campus,Capital Medical University

P2, N=39, Recruiting, SWOG Cancer Research Network | Trial completion date: Aug 2027 --> Aug 2032 | Trial primary completion date: Aug 2026 --> Aug 2028

To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent...ACHM-025 was significantly more effective than cyclophosphamide both as a single agent and when used in combination with cytarabine/6-mercaptopurine. Notably, ACHM-025 in combination with nelarabine was curative when used to treat a chemoresistant T-ALL PDX in vivo. The in vivo efficacy of ACHM-025 directly correlated with AKR1C3 expression levels, providing a predictive biomarker for response. Together, our work provides strong preclinical evidence highlighting the potential of ACHM-025 as a targeted and effective therapy for aggressive forms of T-ALL.

NPM1 MRD positive patients receiving nonmyeloablative conditioning or reduced-intensity conditioning (RIC) without melphalan (mel) had increased risk of relapse or death compared to patients receiving myeloablative conditioning or RIC with mel, regardless of FLT3-ITD co-mutational status (3yrs: relapse 87% vs 55%, P=0.006; OS 15% vs 42%, P=0.013). In patients with NPM1 mutated AML from the Pre-MEASURE study, we show that detection of residual NPM1 variants in pre-transplant blood during CR1 using a highly sensitive DNA-based assay is associated in a dose-dependent manner with a significantly increased risk of relapse and death after allo-HCT, which can be mitigated in part by conditioning regimen. In patients co-mutated for both FLT3-ITD and NPM1 at diagnosis, NPM1 should be prioritized as a target for NGS-MRD if only one test is available.

Several patients with prior melphalan exposure have SBS99 evident in several biopsies, consistent with single cell expansion from MM cells surviving transplant and subsequently seeding in multiple sites... PMD and EMD demonstrate multiple features of genomic complexity when compared with BM-based myeloma, which include emerging copy number aberrations, mutational burden and complex structural variants. EMD are more complex in general than PMD, while IMD shows only trends to increased genomic aberration compared with BM. Ongoing analyses include an expansion in WGS samples, and correlation of genomic features with clinical response to therapy.

P3, N=389, Completed, Fondazione EMN Italy Onlus | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2024

P3, N=430, Not yet recruiting, The First Affiliated Hospital of Soochow University

LC decreased the ROS level in the LC+CP group compared to the CP group (p 0.001). Findings suggest that LC can scavenge the ROS caused by CP and modulate the apoptotic pathway via downregulating the Bax and Caspase3 genes and upregulating the Bcl2 gene in oocytes of mice exposed to CP.

Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=7, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Completed | N=100 --> 7 | Trial completion date: Dec 2025 --> Jul 2024 | Trial primary completion date: May 2025 --> Jul 2024

The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study.

Furthermore, caulerpin or a p53 inhibitor (pifithrin-α) modulated CTX-induced M1 polarization in macrophages, thereby delaying GC senescence. These findings demonstrated that caulerpin contributes to alleviating CTX-induced ovarian toxicity by modulating M1 macrophage polarization through the p53/NF-κB signaling pathway, which promotes the senescence of GCs by inducing ROS production.Thus, caulerpin may be a potential therapeutic strategy for breast cancer patients.

P2, N=29, Not yet recruiting, University of Alabama at Birmingham | Initiation date: Jun 2024 --> Nov 2024 | Trial primary completion date: Oct 2025 --> Jan 2026

Moreover, a noteworthy decrease in the tumor volume was noticed in the mice treated with TNPs along with lower serum toxicity biomarker levels compared to the free drugs. Overall, the developed TNPs proved to be a promising and safer strategy for inducing triple-hit action in TNBC management.

CD4+CD8- T-LGLL is very rare in clinical practice, and its clinical manifestations are different from those of CD4-CD8+ T-LGLL.

This study aims to evaluate the systemic immunomodulatory effects of DALI02 and DALI02 + Prebiotics on cyclophosphamide-induced immunosuppressed rats...These results suggested that the intervention with DALI02 and DALI02 + Prebiotics effectively modulated the structure of the gut microbiota, and DALI02 + Prebiotics restored the dysregulation of SCFAs. In summary, DALI02 and DALI02 + Prebiotics possess immunomodulatory functions, with the latter showing superior effects.

ddNAC affected the levels of systemic peripheral immune markers. However, monitoring these markers may not be useful for predicting responses to ddNAC.

The patient experienced tumor pseudoprogression/progression after three cycles of maintenance temozolomide/TTFields therapy and again after a further two cycles of procarbazine/CCNU/TTFields therapy, and was then switched to CCNU/TTFields therapy. This patient case is reflective of the EF-14 study outcome using TTFields therapy beyond first progression concomitantly with chemotherapy. The observations from this case suggest that TTFields therapy concomitant with CCNU is a valuable treatment modality in patients with GBM, in this context.

P1, N=22, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=16 --> 22

ROR1 CAR T cells were well tolerated in most patients. Antitumor activity was observed in CLL but was limited in TNBC and NSCLC. Immunogenicity of the CAR and lack of sustained tumor infiltration were identified as limitations.

Thus, our data indicate a possible function of TAF7 in the regulation of SSCs and spermatogenesis following downregulation by Busulfan. These findings may account for the therapeutic effects of Busulfan and underlie its potential impact on cancer chemotherapy prognosis.

Furthermore, CPE improved the diversity of intestinal microbiota and increased the abundance of Candidatus_Saccharimonas, Psychrobacter, and Enterorhabdus, which promoted the proper functioning of the intestines. These findings suggest that CPE effectively ameliorates Cy-induced intestinal damage by enhancing the intestinal barrier, improving immune function, and restoring intestinal microbiota.

P2, N=118, Completed, Beth Israel Deaconess Medical Center | Active, not recruiting --> Completed

In conclusion, anthracycline followed by docetaxel improved outcome compared with DC in patients with TOP2A normal early breast cancer, and no clinical value of TOP2A testing was shown. The risk of HF was doubled in patients receiving anthracycline; however, overall, the risk of HF was low.

The beneficial impact of adding chemotherapy to radiotherapy (PCV: procarbazine, lomustine, vincristine) has also been demonstrated. In grade 4 glioblastoma multiforme (GBM), wild-type isocitrate dehydrogenase (IDH) status showed the best treatment outcomes with temozolomide (TMZ) in patients with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation...Bevacizumab (BEV) monotherapy can improve progression-free survival and maintain the initial quality of life. Despite advancements in GBM treatment, outcomes remain unsatisfactory, with a median survival of 14-16 months. Further research is still needed regarding the systemic treatment of central nervous system gliomas.

P3, N=60, Active, not recruiting, Children's Oncology Group | Trial completion date: Dec 2024 --> Dec 2025

P1, N=12, Not yet recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Besides, it was observed a 21 % diminution in body weight and leukopenia in the HFD + Cy group. Obesity-induced metabolic alterations impair intestinal Mrp2 and Mdr-1 functions, bringing about increments in Cy absorption, leading to toxicity; in addition, the antitumor effectiveness of MCT decreased in obese animals.

P1, N=12, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

However, it was found that Se protects the liver slightly better against CP damage than B. The protective effect of Se and B against the toxic effects of CP on the antioxidant markers SOD, CAT and GPx1 was also investigated in silico. The in silico results were consistent with the in vivo results for SOD and CAT, but not for GPx1.

P=N/A, N=30, Recruiting, McMaster University | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jul 2025