Ibrance (palbociclib)

P1/2, N=320, Recruiting, Pikavation Therapeutics, Inc. | Phase classification: P1 --> P1/2 | N=140 --> 320 | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Oct 2026 --> Apr 2027

Drug sensitivity analysis showed that the DSN1 high expression group was resistant to drugs such as Epirubicin, Cyclophosphamide, Ribociclib, and Palbociclib, but relatively sensitive to tamoxifen and lapatinib. DSN1 contributes to breast cancer progression by modulating cell cycle pathways, making it a potential diagnostic and therapeutic target with clinical applicability.

Validating the genome-wide analyses, we found that resistance of breast cancer cells to the CDK4/6 inhibitor palbociclib conferred by TGFβ stimulation was functionally dependent on SOX4. Collectively, our findings reveal an apparent oncogenic function of TGFβ in promoting cell cycle progression and drug resistance through SOX4, highlighting the pro-tumorigenic role of TGFβ signaling in breast cancer progression.

P=N/A, N=6097, Active, not recruiting, Brigham and Women's Hospital | Trial completion date: Oct 2025 --> Mar 2026 | Trial primary completion date: Oct 2025 --> Mar 2026

Tumor histology affects the real-world effectiveness of first line ET plus CDK4/6i. In ILC, all three CDK4/6i performed similarly; therefore, treatment selection should prioritize tolerability, manageability, drug-drug interactions, and patient preferences.

SRT-1720 induces oxidative stress and apoptosis in leukemic lymphocytes through SIRT1-independent pathway(s). In contrast, it enhances antioxidant defense in normal lymphocytes through a SIRT1-dependent pathway. These findings highlight the potential of SRT-1720 as an adjuvant to chemotherapy in T-ALL, particularly in drug combinations demonstrating strong synergism, which may allow dose reduction and decreased toxicity.

Data were leveraged from preclinical and phase I/II studies in metastatic and early breast cancer, as a single agent and with palbociclib, to inform giredestrant dose selection. Our learnings challenge the MTD paradigm in drug development, particularly in targeted therapies, and demonstrate the importance of basing dose selection on the totality of evidence, including preclinical data, and may help inform the clinical development of future targeted therapies.

P1, N=396, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2026 --> Jun 2027

The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).

We conducted a prospective observational study including patients with HR+/HER2- mBC treated with palbociclib, ribociclib, or abemaciclib across three oncology units between 2019 and 2024. Proactive toxicity management and timely dose adjustments are essential to sustain treatment benefit. Dose reductions may even improve outcomes, underscoring the value of individualized dosing strategies.

One of the most prominent milestones in the approach to targeting the cancer cell cycle was the development and approval of CDK4/6 inhibitors such as palbociclib, ribociclib, and abemaciclib. In this article, we focus on heterogeneous vulnerabilities of cancers as consequences of various genetic and epigenetic alterations in the cell cycle-regulatory network, and we discuss how next-generation cell-cycle-targeting drugs currently in the developmental pipeline could exploit these heterogeneous vulnerabilities in the cancer cell cycle. We hope to provide a forward-looking perspective on directions for therapeutic cell-cycle targeting in the advent of personalized precision medicine.

To explore this, we developed palbociclib- (2PR, 9PR, TPR) and abemaciclib- (2AR, 9AR, TAR) resistant ER+ breast cancer sublines through prolonged drug exposure over six months. Additionally, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) was strongly upregulated in palbociclib-resistant cells. Together, these findings identify a distinct, non-canonical senescence phenotype associated with CDK4/6i resistance and may provide a foundation for identifying new vulnerabilities in resistant ER+ breast cancers through targeting SASP-related signaling.