P4, N=96, Recruiting, Bahria University | Active, not recruiting --> Recruiting

Oral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure.

Linked to these disputes is another: whether therapy with hydroxyurea promotes acute leukemia in disorders with a substantial possibility of longevity...Most of these changes, however, conflicted with prior well-validated, phenotypically driven diagnostic criteria and the management of these disorders. The aim of this review is to examine these conflicts and demonstrate how genomic discoveries in myeloproliferative neoplasms can be used to effectively complement the known phenotypic features of these disorders for their diagnosis and management.

P1, N=30, Recruiting, Northwestern University | Active, not recruiting --> Recruiting

The interactions of AIF with RRM1 protein were confirmed by molecular docking and dynamics simulation. Therefore, AIF enhances gemcitabine efficacy against PDAC through the regulation of P53 and RRM1.

P4, N=96, Active, not recruiting, Bahria University | Not yet recruiting --> Active, not recruiting

P=N/A, N=40, Recruiting, Ann & Robert H Lurie Children's Hospital of Chicago | Trial completion date: Jun 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P=N/A, N=68, Active, not recruiting, Ann & Robert H Lurie Children's Hospital of Chicago | Trial primary completion date: Nov 2023 --> Dec 2024

Furthermore, bifonazole exhibited antitumor effects on ESCC patient-derived xenograft (PDX) models by decreasing RRM2 expression and the dNTP pool. In summary, this study reveals the interaction network among HuR, RRM2, and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.

Management included observation in 6 (46.3%), hydroxyurea in 3 (23.1%), imatinib in 3 (23.1%) and Interferon-α (IFN-α) in 1 (7.7%) patients. Effective management of newly diagnosed CML-CP during pregnancy is contingent on the trimester of presentation. Further research and collaboration are warranted to develop standardised guidelines for managing pregnancy-associated CML, particularly in LMICs.

L6 exhibited the highest potency against skin cancer A431 cell line, with an IC50 of 0.19 μM compared to 1.8 μM with triapine and showed low toxicity against PNT-2 cells with an SI index of >100 μM. Also, it lowered the ERK1/2 expression, which affected the caspase 3 activity and showed higher binding affinity compared to the FDA-approved drug Lenalidomide in molecular docking studies. Our findings demonstrated the possible future anticancer drug potency of L6 in the skin cancer A431 cells.

Our study highlights the role of ATM/Rb/E2F1 pathway in controlling cell cycle arrest and apoptosis in response to RRM2 inhibition-induced DNA damage. This provides insight into the therapeutic benefits of COH29 and suggests targeting this pathway as a potential treatment for ATRT.

Antiplatelet therapy was started with acetylsalicylic acid 100 mg and clopidogrel 75 mg once a day. With the recommendation of hematology, cytoreductive treatment, hydroxyurea 1000 mg twice a day, was started. The patient's complaints were resolved at the end of the second day, and the patient with minimal ataxia was discharged with recommendations. Patients with ET should be aware of ischemic cerebrovascular disease and consider antiplatelet and cytoreductive treatment options.

P1, N=30, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting

The use of combination therapies, such as hydroxyurea alongside diltiazem, suggests more efficient and effective MG management compared to monotherapy. Since the efficacy of traditional therapies is limited in most cases due to resistance mechanisms in CSCs, further studies on the biology of CSCs are warranted to develop therapeutic interventions that are likely to be effective in MG. Consequently, improved diagnostic approaches may lead to personalised treatment plans tailored to the specific needs of each patient.

P4, N=96, Not yet recruiting, Bahria University

P2, N=64, Completed, Vanderbilt University Medical Center | Active, not recruiting --> Completed | Trial completion date: Jan 2027 --> Nov 2023

Treatment with phlebotomy, hydroxyurea, and aspirin resulted in significant improvements in ocular symptoms and hematological parameters within 60 days. CONCLUSIONS This case underscores the critical role of primary care in the early detection of polycythemia vera. Timely identification and appropriate referral from primary care settings are essential to avoid diagnostic delays and ensure effective management, improving patient outcomes and preventing complications.

In aging human skin, RRM2B was also found to be more abundant in the dermis and epidermal basal layer than other proteins. Therefore, RRM2B may serve as a clinical marker to identify senescent skin cells.

P4, N=220, Recruiting, Vanderbilt University Medical Center | Not yet recruiting --> Recruiting

We conclude that short-term HU treatment entails differentiation of erythroid progenitor cells and alters the characteristics of LSC in CML. The results imply that studies of LSC and progenitor populations in CML should take effects of initial HU therapy into account.

P1, N=30, Recruiting, Northwestern University | Not yet recruiting --> Recruiting

P4, N=220, Not yet recruiting, Vanderbilt University Medical Center

P4, N=300, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2024 --> Jun 2026

Hyperleukocytosis is a life-threatening hematologic emergency. Early recognition and intervention including cytoreduction, blood product support, antibiotics, and renal replacement therapy may help mitigate the risk of morbidity and early mortality.

P=N/A, N=98, Completed, Pfizer | Recruiting --> Completed | N=150 --> 98

"DM-like" skin eruptions as a long-term consequence of hydroxyurea therapy are possibly not chemotherapy-associated benign toxic changes, but rather inflammatory reactions to complex keratinocyte alterations that clinically mimic the picture of DM. Synergistic mutagenic effects of hydroxyurea and sunlight might be responsible for this unique drug side effect and could provide a pathogenic link to the known increased risk of skin cancer in these patients.

All were treated with imatinib and hydroxyurea and attained major molecular response after 2-7 months. She was treated with dasatinib but no hematologic or molecular response was attained after 6 months despite good compliance. In conclusion, BCR∷ABL1 and JAK2V617F may rarely coexist in MPN with variable temporal evolution, clinicopathological profile, and treatment response.

Importantly, in contrast to the Fe(III) complexes of the clinically trialed thiosemicarbazones Triapine, COTI-2, and DpC, the Fe(III) complexes of PPTP4c4mT and PPTP4c4mSe did not induce detrimental oxy-myoglobin oxidation. This latter effect probably promoted their antiproliferative activity. Both ligands down-regulated multiple key receptors that display inter-receptor cooperation that leads to aggressive and resistant breast cancer.

Our findings highlight the potential utility of RRM2 expression as a biomarker for diagnosing and predicting prognosis in LUAD, shedding new light on the role of RRM2 in this malignancy.

The predicted drugs with high sensitivity to feature genes were CDK1: Ribavirin (0.476), CCNB2: Hydroxyurea (0.474), Chelerythrine (0.470), and KIF11: Ribavirin (0.471). This study identified two subtypes of LUAD, with cluster-1 being more suitable for immunotherapy. These results provided a reference for the development of precision immunotherapy for LUAD patients.

P=N/A, N=50, Completed, Columbia University | N=100 --> 50

Administered intraperitoneally in a mixture of 10% Solutol HS 15/10% ethanol, BM7 exhibited no visible toxicity and significantly reduced tumor weight, comparable to standard drugs imatinib and hydroxyurea. These findings position BM7 as a candidate of significant interest for cancer therapy. Its ability to not only induce apoptosis but also modulate cellular processes such as ROS levels and immune responses, specifically IL-6 suppression, makes BM7 a versatile and promising agent for further exploration in the realm of cancer treatment.

P=N/A, N=30, Recruiting, University Hospital, Strasbourg, France

P1, N=29, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P2, N=98, Completed, Muhimbili University of Health and Allied Sciences | Unknown status --> Completed | Phase classification: P4 --> P2

P=N/A, N=900, Not yet recruiting, New York University | Initiation date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2027 --> Apr 2028

Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.

Together, our results demonstrate that selective RRM2 inhibition induced radiosensitivity of metastatic pNETs both in vitro and in vivo. Therefore, treatment with the selective RRM2 inhibitor, 3-AP, is a promising radiosensitizer in the therapeutic armamentarium for metastatic pNETs.

The sterile alpha motif and histidine-aspartate (HD) domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several haematological malignancies. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.

P1, N=30, Not yet recruiting, Northwestern University

The present study emphasizes the prospect of designing a potential 1,10-phenanthroline hydroxamic acid derivative as a novel dual HDAC and RR-inhibiting anti-cancer molecule.