P1, N=85, Terminated, Boundless Bio, Inc. | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

Secondary prevention included dual antiplatelet therapy, therapeutic phlebotomy, and cytoreductive therapy with hydroxyurea...Long-term outcomes depend on integration of standard acute coronary syndrome therapy with disease-specific cytoreductive strategies to reduce recurrent thrombosis. This case reinforces that acute coronary syndromes should not be routinely attributed to atherosclerotic disease when clinical and angiographic features are disproportionate to traditional risk profiles.

P1, N=21, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2027

Prior Hydroxyurea (HU) use was independently associated with secondary malignancy (OR = 2.73; 95% CI 1.33-5.61; p = 0.006), alongside age and leukocytosis...Cytoreductive therapy was associated with reduced thrombotic risk, while HU exposure was linked to secondary malignancies and disease progression, probably reflecting a high disease burden in the latter. This underscores the need for refined risk stratification and long-term surveillance in LR-PV.

Phase III data from PROUD-PV (NCT01949805; EudraCT, 2012-005259-18) and its phase IIIb extension, CONTINUATION-PV (NCT02218047; EudraCT, 2014-001357-17), demonstrate that ropeg, compared with hydroxyurea, achieves hematologic response more slowly but provides greater, more durable responses after ∼18 months, underscoring the importance of long-term adherence. Early adverse events can challenge adherence, emphasizing the need for proactive symptom management. This review offers evidence- and experience-based perspectives on long-term ropeg treatment and adverse event management to support adherence and maximize therapeutic benefit in PV.

Stable NF1 knockdown ovarian cancer models showed that NF1 depletion did not affect basal proliferation but increased sensitivity to hydroxyurea-induced replication stress, accompanied by increased γH2AX accumulation. Together, these findings indicate that NF1 loss defines a DNA damage-associated mutational and cellular state in ovarian cancer. Rather than acting as a direct prognostic determinant, NF1 mutation appears to increase vulnerability to replication stress and DNA damage, providing functional insight into its role in ovarian tumor biology.

P2, N=30, Not yet recruiting, Georgetown University

The clinical course was complicated by intermittent hydroxyurea non-adherence with marked hematocrit fluctuations; dose optimisation from 1 g to 2 g daily achieved stable hematological control...Whether KMT2C p.Tyr987* contributes causally to the erythroid-biased expansion or represents an accompanying clonal event warrants functional investigation. Comprehensive genomic profiling is essential when canonical driver mutations are absent, and strict adherence to cytoreductive targets remains critical to prevent thrombotic complications.

This case highlights the limitations of routine assays focused on common CALR mutations and supports comprehensive sequencing-based approaches for detecting rare CALR variants. Expanded molecular testing may improve diagnostic accuracy and clinical classification in MPNs.

Dasatinib induced deep molecular remission; however, persistent thrombocytosis required hydroxyurea. This case underscores the importance of vigilance for secondary myeloproliferative neoplasms (MPNs) and clonal evolution when a new hematologic phenotype emerges in a patient with an established MPN. The coexistence of JAK2 V617F and BCR::ABL1 mutations is exceedingly rare and presents significant diagnostic and therapeutic challenges.

P=N/A, N=900, Recruiting, New York University | Trial primary completion date: Apr 2028 --> Jun 2027

Here, we rigorously test this model by simultaneously mapping the transcriptome and genome-wide DSBs induced by six replication stress induders with diverse mechanisms of action (hydroxyurea, methyl-methane sulfonate, camptothecin, actinomycin, doxorubicin and methotrexate). Our data provide support for a model where DSBs are driven by replication inhibitor-induced replication-transcription conflict. More importantly, they reveal active transcription histone markers as the impediments for replication fork progression, therefore a direct culprit for DSBs.