CCND1 mutation

P1/2, N=30, Completed, Yonsei University | Active, not recruiting --> Completed

P2; Trial primary completion date: Jun 2024 --> Dec 2024

P2, N=53, Active, not recruiting, Gynecologic Oncology Group | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

The role of high-risk HPV 16/18 is concurred in the present study strongly in correlation to p16 as a surrogate marker. Moreover, the other driver mutations of Cyclin D1, p53, and EGFR are also implicated as cumulative molecular events in tumor progression as mostly seen in higher Grades.

P and B-MCL have the highest degree of aneuploidy and exhibit an immune cold tumor microenvironment. Further studies are ongoing to refine the molecular differences among B and P-MCL compared to C-MCL.

In this study, we investigated the application of Pomalidomide combined with Obinutuzumab and covalent BTKi (Ibrutinib and Zanubrutinib) for the treatment of TP53 mutated MCL to provide a new treatment evidence for clinical practice. The most common grade 3-4 adverse events were neutropenia (in 5 [35.7%] of 14 patients), thrombocytopenia (in 3 [21.4%] of 14 patients), infections (in 2[14.3%] patients), severe Covid-19 infection was in 2[14.3%] patients. Conclusions Our results provide preliminary evidence that the triplet combination of Obinutuzumab, pomalidomide, and covalent BTKi is an active regimen in MCL patients with the mutation of TP53, and should be evaluated in a prospective randomized controlled trial.

P1/2, N=30, Active, not recruiting, Yonsei University | Trial completion date: Aug 2022 --> Aug 2024 | Trial primary completion date: Aug 2022 --> Aug 2024

P2; Trial primary completion date: Jun 2023 --> Jun 2024

This is the first reported case of a patient with the co-existence of MM, PTC and ccRCC undergoing chemotherapy with a favorable prognosis. Herein, we suggest that such a combination may be non-random, as for mutation of BRAF might account for the co-occurrence of PTC and MM, while mutations of CCND1 and MYC cause the coexistence of MM and ccRCC. This finding may provide valuable guidance on the diagnosis and treatment of such disease, as well as the prevention of developing a second or third tumor for patients with a single primary.

Combination therapy with CDK4/6 inhibitors and EGFR-TKIs may be a promising approach.

We identified amino acid residues in cyclin D1 that may play key roles in the ADκ-cyclin D1 interaction. A nuclear localization antibody against cyclin D1 (NLS-ADκ) was constructed and successfully expressed in breast cancer cells. NLS-ADκ exerted tumor suppressor effects via blocking the binding of CDK4 to cyclin D1 and inhibiting phosphorylation of RB. The results presented here demonstrate anti-tumor potential of intrabody-based cyclin D1-targeted breast cancer therapy.