P=N/A, N=90, Recruiting, West China Second University Hospital

To prevent thrombosis in patients with polycythemia vera (PV), achieving a complete hematologic response (CHR) is highly recommended in practice. In the subgroup analysis, patients with hydroxyurea resistance or intolerance, and those who were hydroxyurea-naïve, had similar results in terms of the CHR. In conclusion, CHR and MR were observed to be associated in patients with PV treated with ropeginterferon.

After informed consent, 21 of them received HU cytoreduction for 14 days before starting TKI treatment (HU group), whereas the other 24 patients received frontline TKI therapy without HU pre-treatment (TKI group). Our findings showed that: (i) there is no benefit from HU cytoreduction in patients affected with chronic myeloid leukemia before starting treatment with TKIs; (ii) any kind of therapy administered before a confirmed diagnosis of chronic myeloid leukemia might change the amount of BCR::ABL1 expression levels.

P1, N=26, Not yet recruiting, Roswell Park Cancer Institute

The potential oncogenic effects of RRM2 in gynecologic tumor cell lines were further demonstrated using the RRM2 inhibitor Triapine (3-AP). These pro-tumorigenic effects may then be mediated through the involvement of RRM2 in the p53 and Akt/mTOR signaling pathways, altering the expression of p53 and Akt/mTOR. Thus, RRM2 is potentially a candidate gene for the unified diagnosis of cervical, endometrial, and ovarian cancers.

Our findings show that combined inhibition of RNR and WEE1 was effective against Ewing's sarcoma in vitro. They thus provide a rationale for the evaluation of the potential of combined targeting of RNR and WEE1 in Ewing's sarcoma in vivo.

P1, N=100, Active, not recruiting, Children's Hospital Medical Center, Cincinnati | Recruiting --> Active, not recruiting

P1, N=42, Active, not recruiting, Boundless Bio | Recruiting --> Active, not recruiting | Trial completion date: Feb 2027 --> Sep 2025 | Trial primary completion date: Feb 2027 --> Sep 2025

P=N/A, N=900, Recruiting, New York University | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Jul 2024

P1, N=12, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025

His treatment included hydroxyurea, which was discontinued because of side effects, and anagrelide, which was unsuccessful in controlling his platelet count...Lacosamide was administered to control the seizures...There have been no reports of epileptic seizures associated with ET in palliative medicine. Therefore, this case report is novel and useful for psychiatrists engaged in palliative care medicine and liaison consultation psychiatry.

The patient was managed with anticoagulation (apixaban) and cytoreductive therapy (hydroxyurea). This case emphasizes the importance of considering underlying MPNs in young patients presenting with unusual thrombotic events, and highlights the significance of early diagnosis and targeted treatment in improving patient outcomes.

Essential thrombocythemia is a rare clonal myeloproliferative neoplasm associated with an increased risk of venous and arterial thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. Based on individual risk factors for thrombosis, persons with essential thrombocythemia may be treated with low-dose aspirin, either alone or in combination with a cytoreductive drug such as hydroxyurea.

Herein, we devise a live-cell microscopy-based approach to follow hydroxyurea-induced fork stalling and subsequent restart at 30 s resolution...E3 ligase RAD18 was recruited at stalled replication forks in parallel to PCNA removal. Our results shed light on fork dynamics during nucleotide depletion and provide a valuable tool for interrogating the effects of replication stress-inducing anti-cancer agents.

In this retrospective study, we analyzed the molecular landscape of 121 ET patients first-line treated with hydroxyurea (n=86) or pegylated interferon (n=35)...None of the patients receiving peg-IFN therapy progressed to myelofibrosis, while 16/86 patients (19%) treated with HU developed secondary myelofibrosis. In conclusion, our results suggest that the presence of at least one additional mutation at diagnosis is associated with failure to achieve CR and is also associated with an increased risk of hematologic evolution.

While AOH generally suppressed a drug-induced activation and increased anti-inflammatory IL10 levels, DON potentiated activation and pro-inflammatory markers, such as CXCL8 and TNF in immune cells. In conclusion, AOH and DON have the potential to alter the immunological effects of anticancer therapies, which should be considered during therapy as well as in their future risk assessment.

P=N/A, N=68, Active, not recruiting, Ann & Robert H Lurie Children's Hospital of Chicago | Trial completion date: Feb 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

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.