RB1 positive

P1a/1b, N=9, Terminated, Shengke Pharmaceuticals Pty Ltd | N=67 --> 9 | Recruiting --> Terminated; The reasons for early termination is due to slow recruitment

Because clinical behavior and therapeutic options of tMF and primary cutaneous ALCL may be different, it is clinically relevant to differentiate these 2 entities. The proof of clonal relationship may be useful in diagnostically challenging cases with features overlapping between tMF and primary cutaneous ALCL.

The intracellular inhibition of CDK4/6 by 17m was confirmed by western blot analysis of the levels of phosphorylated Rb in MDA-MB-453 cells. With respect to the metabolic stability, compound 17m possessed longer half-life (t) in mouse liver microsome than palbociclib.

Our data demonstrated that RB1 was effective for immunohistochemically investigating the MCPyV status of tumors. TPS was superior to the combined positive score in evaluating PD-L1 in MCC. Tumor-infiltrating lymphocytes were the only parameters that were associated with survival. Further studies with larger series are required to confirm these results.

FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS.

RPR is a practical and effective prognostic marker in newly diagnosed patients with MM, and a high RPR is an independent poor prognostic factor.

P1a/1b, N=67, Recruiting, Shengke Pharmaceuticals Pty Ltd | Active, not recruiting --> Recruiting

P1a/1b, N=9, Active, not recruiting, Shengke Pharmaceuticals Pty Ltd | Recruiting --> Active, not recruiting | N=67 --> 9

BET inhibitor resistance in RB-deficient cells is abolished by co-administration of CREB inhibitor. Our study identifies RB protein as a bona fide intrinsic inhibitor of BRD4 and demonstrates that RB inactivation confers resistance to small molecule BET inhibitors, thereby revealing a regulatory hub that converges RB upstream signaling onto BRD4 functions in diseases such as cancer.

P2, N=124, Completed, Pfizer | Active, not recruiting --> Completed

Together, our data suggest that CDK4/6 inactivates Rb to begin E2F and CDK2 activation, and high CDK2 activity is necessary and sufficient to generate a bistable switch for Rb phosphorylation before DNA replication. These findings highlight how cells initiate the cell cycle and subsequently commit to the cell cycle before the G1/S transition.

P2, N=27, Terminated, Dana-Farber Cancer Institute | Trial completion date: Nov 2025 --> Jan 2022 | Active, not recruiting --> Terminated; Slow accrual

Change in KIFC1 expression is primarily driven by ABE in Rb-positive TNBC cells. DOX increases ABE speed to achieve a full inhibition of KIFC1 in Rb-positive, yet, without influencing its expression in Rb-negative TNBC cells.

P2, N=124, Active, not recruiting, Pfizer | Unknown status --> Active, not recruiting | Trial completion date: Dec 2019 --> Sep 2022

SOX2 diffuse expression was observed in 92% of the MCC cases and almost never observed in non-neuroendocrine skin epithelial neoplasms (2%, p < 0.0001, LHR +  = 59). Furthermore, SOX2 diffuse staining was more frequently observed in MCCs than in extra-cutaneous NECs (30%, p < 0.001, LHR +  = 3.1).These results confirm RB1 as a robust predictor of MCC viral status and further suggest SOX2 to be a relevant diagnostic marker of MCC.

Long-term follow-up of the father will include periodic evaluation of the eyes and orbits, and surveillance for systemic sarcoma and secondary malignancies. Implications for unaffected individuals need to be further studied.

P2, N=37, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Nov 2021 --> Aug 2021

P2, N=37, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting

P1a/1b, N=67, Recruiting, Shengke Pharmaceuticals Pty Ltd | Not yet recruiting --> Recruiting

Especially we confirmed that VRN081569 induces caspase 3/7 activity faster in Rb1-negative cells (~50-fold EC50 of caspase 3/7 activity compared to Rb1-positive cells), and cell cycle analysis has shown that our compound induces a dose-dependent dysregulation of mitosis, resulting in a decrease in the frequency of the G0/G1 phase, and also induces aneuploidy and apoptosis. Finally, we confirmed a combination effects with anti-microtubule agents BCL-2 inhibitor and PARP-1 inhibitor, suggesting that modulation of two different cellular processes may overcome the lack of single agent activity for TNBC.

P2, N=37, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2020 --> Nov 2021

P2, N=304, Completed, Abramson Cancer Center of the University of Pennsylvania | Recruiting --> Completed | N=205 --> 304