Ibrance (palbociclib) / Pfizer, Amgen - LARVOL DELTA

Real-world outcomes of targeted endocrine therapies in hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative breast cancer with central nervous system metastases (HOPA 2026) - "Key trials evaluating abemaciclib, palbociclib, ribociclib, inavolisib, alpelisib, elacestrant, and capivasertib either excluded patients with CNS metastases or enrolled them in low numbers, where intracranial efficacy could not be reported. Results are pending and will be available at the time of the presentation."

Clinical • Real-world • Real-world evidence • Breast Cancer • CNS Tumor • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Impact of GLP-1 Receptor Agonists in Hormone Receptor-Positive Breast Cancer Patients Receiving CDK4/6 Inhibitors (HOPA 2026) - "Three cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors- abemaciclib, palbociclib, and ribociclib- have been approved by the United States Food and Drug Administration as first-line treatment for advanced or metastatic HR+, HER2- breast cancer...Obesity and type 2 diabetes, present in approximately 40% of U.S. adults, are associated with increased breast cancer risk, recurrence, and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, tirzepatide, dulaglutide, exenatide and liraglutide, are increasingly prescribed for these comorbidities due to their efficacy in weight reduction, glycemic control, and cardiovascular risk mitigation... Data collection and analysis are in progress."

Clinical • Breast Cancer • Diabetes • Eye Cancer • Genetic Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Metabolic Disorders • Obesity • Oncology • Retinal Disorders • Solid Tumor • Type 2 Diabetes Mellitus • HER-2

Prognostic Impact of Early Metabolic Response on Interim 18F-FDG PET/CT in HR+/HER2- Metastatic Breast Cancer Treated with CDK4/6 Inhibitors. (PubMed, Medicina (Kaunas)) - " This two-center retrospective study included 203 patients with HR+/HER2- MBC who received first-line CDK4/6 inhibitors (ribociclib or palbociclib) plus endocrine therapy between 2018 and 2024. Although the predictive accuracy of ΔSUVmax alone was modest, the strong survival gradient suggests meaningful prognostic value. Prospective studies with standardized imaging time points and comprehensive metabolic metrics are warranted to define the role of PET-guided treatment adaptation."

Journal • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

Targeting Aurora A kinase together with alternative survival signaling overcomes resistance to endocrine and CDK4/6 therapies in ER+ breast cancer (AACR 2026) - P2 | "A recent phase II trial (NCT02860000) reported clinically meaningful benefit of the AURKAi, alisertib (ALS), in advanced, endocrine-resistant ER+ BC. Identifying biomarkers and key signaling pathways involved in AURKA inhibition is essential to optimize ALS use and guide effective combination strategies to enhance sensitivity and overcome resistance in ER+ BC. ER+ BC cell models naïve or resistant (R) to various ET (EndoR) and/or palbociclib (PalboR, a CDK4/6i) were used...In the tamoxifenR/PalboR model and its ALSR derivative, in line with the signaling changes, EGFRi, pan-HERi (Neratinib, Nrb), or MEKi together with tamoxifen+Palbo+ALS showed strong efficacy. In the dual fulvestrantR/PalboR model, ALS+Nrb was highly effective, and adding Palbo further enhanced this effect, while in its ALSR derivative, fulvestrant+Palbo+ALS+Nrb regimen was needed to achieve substantial growth inhibition. Our findings highlight the potential of combining ALS with AKT, MAPK,..."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AURKA • CDK4 • CDKN1A • ER • PARP1

Axillary Management and Outcomes After Neoadjuvant Endocrine Therapy in the Randomized PELOPS Trial. (PubMed, Ann Surg Oncol) - P2 | "The addition of palbociclib to NET did not impact pathologic nodal outcomes. Among those with ypN+ disease, neither LRRFI nor BCSS appears to be impacted by performance of ALND."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Convergent CDK4/6 and PI3K/mTOR pathway hyperactivation defines a targetable axis in osteosarcoma across RB1-proficient and RB1-deficient contexts (AACR 2026) - "We evaluated palbociclib, voxtalisib, and the combination across RB1+ and RB1- OS models, using cell lines, patient derived xenografts (PDXs), and an experimental metastasis model. In vivo validation studies are ongoing. These findings identify convergent CDK4/6–PI3K/mTOR hyperactivation as a targetable axis in OS and support further evaluation of CDK4/6i-based strategies, including in RB1-deficient disease."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CDK4 • CDKN2A • RB1

Association between area deprivation index (ADI) and treatment persistence (TP) with CDK4/6 inhibitors (CDK4/6i)in HR+/HER2- breast cancer (AACR 2026) - "In MBC, median ADI values were 19 (IQR 11-25) for the less-deprived groups and 47 (IQR 39-62) for the more-deprived groups across agents (abemaciclib, palbociclib, ribociclib). In this large, real-world cohort, TP with CDK4/6i did not differ by neighborhood socioeconomic deprivation. Further work incorporating individual-level social determinants of health may better elucidate drivers of adherence and persistence disparities.Acknowledgment: ChatGPT (OpenAI) was used to assist with text revision and editing for clarity."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

When CDK meets CIP: Linking target engagement to functional outcomes in CDK2 molecular glue and CDK‑TCIP (AACR 2026) - "CCNE amplification conferred heightened sensitivity, while palbociclib resistant cell lines revealed CDK2 MG as a potential strategy to overcome drug resistance... This study provides comprehensive profiling showing that CDK2 MGs and CDK‑TCIPs achieve distinct biological outcomes through degradation versus transcriptional rewiring. By integrating biophysical, biochemical, and cellular analyses, we establish quantitative links between target engagement and phenotypic consequences. These findings define mechanistic frameworks for optimizing CDK‑targeting modalities and inform rational design of selective, context‑dependent interventions in oncology."

Oncology • BCL6 • CDK2 • CDK9 • CRBN

Comparative efficacy of adjuvant CDK4/6 inhibitors in early breast cancer: A hazard ratio-based network meta-analysis using the NetMetaEasy platform (AACR 2026) - "In this hazard ratio-based NMA, abemaciclib and ribociclib significantly improved iDFS compared with endocrine therapy, whereas palbociclib did not. Our findings illustrate the utility of NMA for comparative evaluation in the absence of head-to-head trials."

Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ISM6210, a potent and selective CDK4 inhibitor for the treatment of HR+/HER2- breast cancer (AACR 2026) - "Notably, in human hematopoietic stem cell assays, ISM6210 exhibited an IC50 value about 30-fold higher than the dual CDK4/6 inhibitor Palbociclib against human hematopoietic stem cells, suggesting reduced myelosuppressive potential. In vivo, ISM6210 achieved robust anti-tumor activity at 30 mg/kg BID across multiple HR+ breast cancer xenograft models with notable tumor enrichment.In addition to its robust biological potency and high selectivity, ISM6210 exhibited favorable drug-like properties, including desirable in vitro ADMET profiles, excellent in vivo exposure and clearance, and good oral bioavailability across multiple preclinical species. Collectively, these findings establish ISM6210 as a potent and selective CDK4 inhibitor that delivers strong efficacy and a promising hematologic safety margin for HR+/HER2- breast cancer treatment."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCND1 • HER-2

Nebivolol exhibits cell growth inhibition in drug-resistant HR+/HER2- breast cancer and anti-tumoral synergism with abemaciclib in vitro (AACR 2026) - "Since HR+/HER2- BC is typically treated with endocrine therapy (ET) alone or in combination with CDK4/6 inhibitors (CDK4/6i), we also assessed the effects of nebivolol in ET- and CDK4/6i-resistant models, as well as in combination with ET and CDK4/6i. The efficacy and potency (IC50) of nebivolol were evaluated using MCF7 and T47D parental cells and their estrogen deprivation-resistant (EDR), palbociclib-resistant (PalboR), and EDR/PalboR derivatives. Nebivolol inhibited the growth of HR+/HER2- BC cell lines sensitive or resistant to ET and/or CDK4/6i and synergized with abemaciclib. Ongoing studies are evaluating nebivolol and abemaciclib in other cell-based assays and combination with ET for enhanced therapeutic potential."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Palbociclib (P) in patients (pts) with lung cancer (LC) with CCND1 amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Lung Cancer • Oncology • Solid Tumor • CCND1

A highly selective KAT6/7 dual inhibitor with best-in-class potential and favorable pharmacokinetic profile (AACR 2026) - "In ER+ breast cancer cells, KC1086 durably suppressed H3K23ac/H3K14ac, which outperformed PF-07248144 on biomarker depth and duration...Combinations of KC1086 further demonstrated enhanced efficacy: (i) with Palbociclib (CDK4/6 inhibitor) (TGI 101%) in ZR-75-1 ER+ breast cancer xenograft model; (ii) with Fulvestrant (Estrogen Receptor Antagonist) (TGI 83%) in xxT47D breast cancer models yielding tumor regressions and survival benefit. Furthermore, KC1086 demonstrated favorable PK profile and significant safety window: linear PK, high oral bioavailability, minimum drug accumulation and clean safety pharmacology (eg. CV, CNS and respiratory).In conclusion, we demonstrated equipotent dual inhibition of KAT6/7 delivering potentially deeper chromatin closure than KAT6-selective blockade, which translated into robust monotherapy activity and combination synergy across ER+ breast cancer, ovarian cancer as well as other tumor models, with favorable preclinical safety. These data..."

PK/PD data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HER-2 • KAT6A

The KAT6/7 inhibitor IDE574 disrupts tumor lineage identity and drug tolerance to deliver robust antitumor activity in biomarker selected indications (AACR 2026) - "Consistent with this biology, IDE574 delivered deeper and durable antitumor activity in aggressive ER+ mBC PDX models including ESR1 mutant backgrounds reported to be resistant to the clinical KAT6 inhibitor even when combined with palbociclib and fulvestrant. Pan-cancer cell viability assessments and xenograft studies with IDE574 revealed indication opportunities in addition to mBC, including predictive biomarker-associated subsets of NSCLC and bowel cancer. These preclinical findings combined with favorable drug-like properties and non-clinical safety profile support evaluation of IDE574 in the clinic as a treatment option for patients with biomarker positive disease."

Biomarker • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD133 • CD24 • ER • FOXA1 • GATA3 • KAT6A • KAT6B • KAT8

Discovery and development of a novel PI3K-CDK4/6 dual inhibitor PC-13 for the treatment of breast cancer (AACR 2026) - "Breast cancer continues to be a major cause of cancer-associated mortality globally, underscoring the urgent need for innovative therapeutic strategies. Furthermore, PC-13 exhibits reasonable pharmacokinetic properties and achieves significant tumor growth suppression in a T47D xenograft model, with efficacy comparable to the Palbociclib-Buparlisib combination regimen, while maintaining a promising safety profile. Our findings highlight the potential of concurrent PI3K and CDK4/6 inhibition as a novel and effective therapeutic approach for breast cancer, supporting further development of PC-13 as a clinical candidate."

Breast Cancer • Oncology • Solid Tumor

Discovery of a novel, selective brain penetrant CDK4 inhibitor for targeted cancer therapy (AACR 2026) - "Approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are associated with hematologic toxicity, including neutropenia, linked to CDK6 rather than CDK4 inhibition. AL-0433 is a promising, AI-designed, selective CDK4 inhibitor with broad activity across breast, ovarian, and glioblastoma cell lines. Its favorable PK profile, preclinical efficacy, and rational design strategy support further clinical development"

Brain Cancer • Breast Cancer • Glioblastoma • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CCND1 • CCND3 • CDK1 • CDK2 • CDK9 • CDKN2A

Engaged but not degraded: Proteome-wide CETSA in degrader research (AACR 2026) - "In intact cells, downstream biological effects were also observed; for example, effects on the CDK4/6 substrate RB1 were seen with the CDK4/6-targeting PROTAC BSJ-03-204 and its kinase-binding warhead palbociclib. In contrast, the CDK9-targeting PROTAC THAL-SNS-032 did not affect RB1, whereas its kinase-binding warhead SNS-032 did...Overall, a CETSA-MS workflow can concurrently reveal degradation, target engagement, and downstream biological effects, including liabilities arising from engagement without degradation. This integrated perspective improves selectivity assessment and supports the design and interpretation of degrader campaigns."

Oncology • BRD4 • CDK4 • CDK9 • RB1

C018, a potent and selective CDK4&9 dual inhibitor (AACR 2026) - "Background: CDK4&6 inhibitors have been approved for the treatment of metastatic ER+&HER2- breast cancer, either as monotherapy or in combination with endocrine therapy. Our findings demonstrate that simultaneous inhibition of CDK4 and CDK9 may exert synergistic effects in overcoming palbociclib resistance. CDK4&9 dual inhibition represents a promising therapeutic strategy to overcome both endocrine therapy and CDK4&6 inhibitor resistance in ER+ breast cancer, warranting further clinical development as a novel approach for treating resistant breast cancer."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CCNE1 • CDK2 • CDK9 • ER • HER-2

Synergistic preclinical activity of dual CDK4/6 and mTORC1 inhibition in translocation renal cell carcinoma (AACR 2026) - "Pharmacological inhibition of CDK4/6 activity using palbociclib or abemaciclib, causes cell cycle arrest which was also recapitulated upon genetic knockout of CDK4/6 using CRISPR-Cas9. The combination of palbociclib and RMC-5552 in a tRCC xenograft model showed greater efficacy than either single agent while also being well-tolerated.Conclusions- Our work suggests that combined inhibition of CDK4/6 and mTORC1 activity has therapeutic potential in tRCC. This work may offer rationale for molecularly directed therapies in tRCC, which currently lacks any standard of care."

Preclinical • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CCND1 • TFE3

FOXM1 as a drug target in NF1-associated malignant peripheral nerve sheath tumors (AACR 2026) - "Synergistic killing of MPNST cells was obtained by combining thiostrepton with a MEK inhibitor (mirdametinib), CDK4/6 inhibitor (palbociclib), or EGFR inhibitor (gefitinib), while NB drugs synergized best with gefitinib. Our data demonstrate FOXM1 is an important driver of MPNST pathogenesis. FOXM1 expression and transcriptional activity are greatly increased in MPNSTs compared to benign precursors from the same patients. In agreement, genetic and therapeutic inactivation of FOXM1 promoted MPNST cell arrest and death."

Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • CDKN2A • FOXM1 • NF1

A Tumor-Agnostic, Topology-Informed Scoring Framework for Drug Repurposing: Application to CDK4/6 Inhibitor Resistance in HR+ Breast Cancer. (PubMed, Biomedicines) - "To rigorously validate this framework and overcome the limitations of public bulk datasets, we combined cross-cohort statistical benchmarking with original RNA-sequencing data generated from a laboratory-derived palbociclib-resistant model (MCF7-PR)...In application, the framework identified sorafenib as a top-ranked candidate for reversing CDK4/6i resistance... This study presents TIHS as a mechanism-agnostic, experimentally validated bridge between resistance-state transcriptomes and clinical decision-making. By coupling computational prioritization with in vitro functional verification, we demonstrate that targeting topology-defined hubs is a viable strategy for overcoming therapy resistance."

Journal • Pan tumor • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • FGFR3

Next Frontier in HER2+/HR+ Breast Cancer: Leveraging Cell Cycle Control with CDK4/6 Inhibitors. (PubMed, J Pers Med) - "Preclinical studies have demonstrated synergistic antitumor activity when CDK4/6 inhibitors are combined with trastuzumab, pertuzumab, or newer HER2-targeted agents across multiple HER2+ breast cancer models. In the metastatic setting, phase II trials including MonarcHER and PATRICIA II have shown encouraging efficacy signals, while the phase III PATINA trial demonstrated a clinically meaningful 15.2-month progression-free survival benefit with palbociclib plus anti-HER2 therapy and endocrine therapy...Despite these advances, key challenges remain including the identification of predictive biomarkers, optimal treatment sequencing, and the integration of emerging HER2-targeted agents such as trastuzumab deruxtecan. Novel CDK4/6 inhibitors including dalpiciclib and next-generation agents are expanding therapeutic options, while combination strategies incorporating CDK7 inhibition represent future therapeutic frontiers. The evolving landscape of HER2+/HR+ breast cancer..."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCND1 • ER • HER-2

Breast Cancer Patient Attitudes Towards Oncology Drug Costs in Ireland. (PubMed, Curr Oncol) - "92.2% (N = 166/180), 87.8% (N = 158/180) and 68.9% (N = 124/180) of participants found the costs of pembrolizumab, palbociclib and trastuzumab respectively to be unacceptable. There was a statistically significant difference in patient desires to be better informed of societal drug costs between those with early-stage breast cancer and those with metastatic disease (75.8% vs. 47.4%, χ2 = 6.923, p = 0.009). These findings indicate that many Irish patients with breast cancer find the societal costs of oncology medications to be unacceptable, and many patients have a desire to be better informed of these costs."

HEOR • Journal • Breast Cancer • Oncology • Solid Tumor

Apoptosis-inducing factor mitochondria-associated 2 (AIFM2) functions as an oncogenic driver and prognostic biomarker in oral squamous cell carcinoma (AACR 2026) - "AIFM2 knockdown reduced migration and invasion, while overexpression enhanced proliferation, migration, and invasion but had minimal impact on sensitivity to cisplatin, palbociclib, or cold atmospheric plasma. Furthermore, the AIFM2-associated gene expression signature generated by the LGBM model effectively stratified patients by prognostic risk. Collectively, these findings indicate that AIFM2 functions as an oncogenic driver in OSCC, promoting tumor progression and poor prognosis, and is epigenetically regulated by tumor-suppressive miR-32-5p and miR-432-5p, representing a potential prognostic biomarker and therapeutic target."

Biomarker • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • AIFM2 • MIR432

Dual-targeting CDK4 and CDK2 overcomes resistance to CDK4/6 inhibitors in HR+ breast cancer (AACR 2026) - "The next generation of CDK inhibitors such as atirmociclib targeting CDK4 and tagtociclib targeting CDK2 have demonstrated encouraging early efficacy, and the combination of a selective CDK4 inhibitor and a selective CDK2 inhibitor has entered clinical trials...These results suggested that CDK4:CDK6 selectivity of Cpd-1308 was greater than that of palbociclib.Further kinetic characterization using surface plasmon resonance (SPR) spectroscopy revealed that Cpd-1308 has long residence time on CDK2 in comparison with tagtociclib...Cpd-1308 indeed showed superior potency on antiproliferation of derived palbociclib resistant MCF7 cells (MCF7-palbo-r) and derived abemaciclib resistant MCF7 cells (MCF7-abema-r)...Cpd-1308 demonstrated significant resistance-overcoming activity.Taken together, we demonstrate activity of Cpd-1308 in HR+ breast cancers and CDK4/6i-resistant breast cancers. Our research results indicate that co-targeting CDK4 and CDK2 with a small-molecule may..."

Breast Cancer • Eye Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Retinoblastoma • Solid Tumor • CD34 • CDK2 • CDK6