tamoxifen / Generic mfg. - LARVOL DELTA

RasGrp1: From Skin to Organoid (AAD 2026) - "Tamoxifen induction was used to map the anatomical location of RasGrp1 in the skin and trace the durability of RasGrp1+ populations during organoid establishment...Our preliminary studies suggest RasGrp1+ populations can be maintained in vitro, enabling future mechanistic studies. Ongoing work includes establishing long-term organoid cultures and quantifying RasGrp1 expression across specific epidermal subpopulations."

Non-melanoma Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • RASGRP1

Protein Kinase C fusions - Rare but Targetable Initiating Mutations in Melanoma? (AAD 2026) - "Small-molecule PKC inhibitors (e.g., LXS196) have demonstrated clinical activity in uveal melanoma, suggesting their potential utility against PKC fusion–driven tumors (4)...To further investigate their role in tumor initiation, we developed a transgenic mouse model in which expression of a PKC fusion gene (ATP2B4::PRKCA) is induced in melanocytes following tamoxifen administration...This model offers an effective system for understanding PKC fusion mediated signaling, evaluating targeted therapies, and studying cooperating genetic events. Collectively, our findings establish PKC fusions as initiating events in melanoma and underscore the importance of continued preclinical modeling to guide translational advances."

Eye Cancer • Melanoma • Nevi and Melanomas • Solid Tumor • Uveal Melanoma • BRAF • GNA11 • GNAQ • PRKCA

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

Opposite regulation of brain and lung metastases by endothelial FAK deletion (AACR 2026) - "In this study, we investigated the function of the cerebral endothelial FAK and compared its contribution to brain metastasis with lung metastasis. We generated tamoxifen-inducible, EC-specific FAK knockout (FAK-cKO) mice (VEcad-CreERT2; FAK-flox/flox) and established brain metastatic (BrM) and lung metastatic (LuM) cell lines from Ex3LL murine lung cancer cell line... Endothelial FAK deletion exacerbated brain metastasis, while reducing lung metastasis. These findings suggest that endothelial FAK differentially regulates vascular barrier functions in the brain and lung, thereby exerting opposing effects on cancer metastasis. Further investigation is required to elucidate the mechanisms by which endothelial FAK preserves BBB integrity and prevents brain metastasis."

Brain Cancer • Lung Cancer • Oncology • Solid Tumor • CD31 • CDH5 • PECAM1 • TNFA

First target disclosure for the preclinical development of ATNM-400, a first-in-class actinium-225 radioconjugate with pan-tumor efficacy in solid tumors (AACR 2026) - "In vivo, ATNM-400 demonstrated sustained tumor uptake with off-target exposure in normal tissues, driving potent anti-tumor activity in:• Prostate cancer: ATNM-400 outperformed androgen receptor (AR) pathway inhibitor enzalutamide, 177Lu-PSMA-617, and 225Ac-PSMA-617, producing durable regressions and complete responses in enzalutamide- and 225Ac-PSMA-617-resistant models.• EGFR-mutant lung cancer: ATNM-400 synergized with EGFR inhibitor osimertinib, achieving complete cures in animals, correlating with increased target expression in osimertinib-resistant models.• Breast cancer: ATNM-400 exhibited tumor regressions in HR+ breast cancer, TNBC and combination activity in estrogen receptor (ER) inhibitor tamoxifen- and HER2 antibody trastuzumab-resistant tumors, correlating with increased target expression. ATNM-400 exhibits robust pan-tumor activity, overcomes resistance to AR, EGFR, and HER2/ER-targeted therapies, and demonstrates a favorable safety profile. These..."

Pan tumor • Preclinical • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer

Comparative analysis of lncRNA detection using qPCR and ddPCR technologies in breast cancer research (AACR 2026) - "Droplet digital PCRTM (ddPCRTM), by contrast, offers absolute quantification without reliance on standard curves and demonstrates superior sensitivity and reproducibility, particularly for rare transcripts.In this study, we compared qPCR and ddPCR platforms for profiling breast cancer associated lncRNAs using an assay panel of up to seven targets in the MCF7 estrogen receptor-positive (ER⁺) cell line and its Tamoxifen-resistant derivative (MCF7-TAMR), including reference genes (HPRT1, RPL13a) from validated panels...Its advanced capabilities make it valuable for detecting rare transcripts such as lncRNAs. Selecting the right method is crucial for accurately measuring new RNA targets and Droplet Digital PCR offers the reliability needed for absolute quantification."

Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HPRT1 • RPL13A

The role of noncoding transcripts in glucose-dependent gene regulation in estrogen receptor-positive breast cancer (AACR 2026) - "Conventional treatments include endocrine therapy that antagonizes ER signaling with tamoxifen or aromatase inhibitors...Currently, we are elucidating LNC16's molecular mechanism by which it regulates gene expression to drive ER+ breast cancer biology using cell- and mouse-based experiments. Collectively, these results suggest that estrogen-regulated transcripts can regulate glucose-dependent gene expression to control ER+ breast cancer phenotypic outcomes."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Development of a stabilized Z-endoxifen topical formulation for breast cancer prevention (AACR 2026) - "Purpose: The primary objective of this work was to develop a pharmaceutically stable, transdermal delivery strategy for Z-endoxifen, the highly potent and bioactive metabolite of tamoxifen. Four distinct topical formulation types were prepared... Instability challenges of Z-endoxifen in a topical formulation were overcome by adding specific antioxidants into varied formulation bases and controlling storage temperature. This advancement enables the development of a more potent and potentially safer localized breast cancer prevention therapy by delivering the highly bioactive Z-isomer and minimizing systemic exposure. Future work will involve in vivo pharmacokinetic/pharmacodynamic studies to confirm localized breast tissue delivery and minimal systemic absorption, paving the way for advanced clinical trials aimed at providing an improved preventative treatment for women at high risk for breast cancer."

Breast Cancer • Oncology • Solid Tumor

Combination of medroxyprogesterone acetate (MPA) and a WEE1 or ATR inhibitor enhances anti-tumor activity of estrogen receptor-positive endometrial cancer cells (AACR 2026) - "Tamoxifen, letrozole, fulvestrant, and medroxyprogesterone acetate (MPA, 25 μM for MFE280; 30 μM for ARK1) were used as hormone therapies. As drugs for targeted therapies, either the ATR inhibitor (ATRi) AZD6738 (2.5 μM) or the WEE1 inhibitor (WEE1i) MK1775 (0.1 μM) was employed... We found that the combination of MPA and ATRi markedly enhances anti-tumor activity in ER+ endometrial cancer, in an ERα expression-dependent manner. Future studies are needed to elucidate the mechanism of these synergistic effects."

IO biomarker • Breast Cancer • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AURKA • CCND1 • ER

Targeting glycogen metabolism in cancer-associated fibroblasts alleviates immunosuppression and inhibits colorectal cancer malignancy (AACR 2026) - "APCf/f; CDX2-Cre/ERT2 mice were injected with tamoxifen to induce adenoma formation... Our results demonstrate that glycogen metabolism is crucial for promoting CAF immunosuppressive functions. Importantly, our findings suggest that targeting glycogen metabolism in CAFs alleviates immunosuppression and inhibits CRC malignancy."

Colorectal Cancer • Oncology • Solid Tumor • CAFs • CDX2 • CXCL6 • HK2 • IL6 • PYGL • SLC2A1 • TGFB1

High dietary cholesterol promotes epithelial-to-mesenchymal transition and invasion in colorectal cancer via the Wnt/Snai2 axis of transcriptional regulation (AACR 2026) - "Tumor growth was induced by intraperitoneal tamoxifen injection... High dietary cholesterol promotes an EMT-like phenotype in CRC, which involves a loss of epithelial gene expression and activation of Wnt signaling. Notably, high cholesterol increases expression of the transcription factor Snai2 (Slug), which is known to be induced by Wnt signaling and to suppress expression of Cldn1, Zo1, and E-cadherin. These findings indicate that high cholesterol promotes EMT in CRC via a Wnt-dependent mechanism of transcriptional regulation, which could potentially increase the risk of invasion and metastasis in CRC patients affected by high cholesterol."

Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CDH1 • CLDN1 • SNAI2 • TJP1

Is endothelial dysfunction induced by aromatase inhibitors reversible after treatment? (AACR 2026) - "Aromatase inhibitors (AIs) are a standard therapy for postmenopausal women with hormone receptor-positive breast cancer, improving disease-free survival compared to tamoxifen... AI therapy is associated with significant and progressive endothelial dysfunction, which does not fully recover after treatment cessation, highlighting the importance of CV monitoring in breast cancer patients receiving long-term AI therapy."

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • IL6 • TNFA

Multifactorial risks for multiple primary cancers (AACR 2026) - "Tamoxifen exposure conferred a 3.5-fold higher uterine cancer hazard with earlier onset yet improved survival... Automated classification of MPC reveals genetic and exposure-related patterns in secondary cancer risk, timing, and survival. Ongoing work is integrating tumor genomics as well as polygenic risk scores to identify inherited and therapy-related drivers of cancer development and aggressiveness. (Supported by MSK Niehaus Center and BCRF)."

Acute Myelogenous Leukemia • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Uterine Cancer

Muscle iron overload contributes to cancer cachexia-induced muscle wasting (AACR 2026) - "Furthermore, muscle-specific deletion of TFRC in muscle using a muscle-specific tamoxifen-inducible Cre mouse line bred to a conditional TFRC floxed mouse line rescued C26-induced muscle wasting. Our work rigorously demonstrates that elevated muscle iron leads to muscle wasting, and this elevated muscle iron in cancer cachexic muscle contributes to cancer cachexia-induced muscle wasting. Current work is being done to test whether elevated muscle iron is seen in human samples and to decipher the mechanisms by which muscle iron overload leads to muscle wasting."

Oncology • Pancreatic Ductal Adenocarcinoma

Short telomeres limit brafV600E driven melanomagenesis in humanized telomere (HuT) mice (AACR 2026) - "Oncogenic BrafV600E was activated in Braf+/LSL-V600E; Tyr::CreERT+/o transgenic mice at 2 months of age via tamoxifen, followed by weekly UV exposure to model chronic sunlight-driven melanoma...These findings demonstrate that short, humanized telomeres suppress BrafV600E-driven melanomagenesis in a genotype-, age-, and sex-dependent manner. The HuT mouse model provides a physiologically relevant platform to investigate telomere-regulated melanoma biology, immune-tumor interactions, and genomic instability, offering valuable insights for preclinical cancer research."

Preclinical • Melanoma • Oncology • Solid Tumor • BRAF • TERF2 • TERT

Chromatin profiling reveals the impact of fulvestrant on estrogen receptor-driven chromatin dynamics in breast cancer cells (AACR 2026) - "Endocrine therapies targeting the ER such as Tamoxifen, Fulvestrant (FULV) and Aromatase inhibitors, are widely used in the clinic. This study provides new insights into the mechanistic impact of FULV on ER activity, highlighting its ability to modulate H3K27ac dynamics even in the absence of transcriptional changes. These findings underscore the complexity of ER signaling and suggest that FULV's therapeutic effects may extend beyond simple antagonism of ER activity."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Design, synthesis, in silico, and biological evaluation of novel pyrazolopyrimidinone-based estrogen receptor inhibitors. (PubMed, Future Med Chem) - "Moreover, western blot was done for compounds 5a and 5b, showed two-fold greater potency than tamoxifen at 10 µM...Finally, molecular dynamics simulations of compounds 5a and 5b were performed to support the stability of the protein-ligand complexes. Compounds 5a and 5b showed remarkable activity toward tumors which have higher estrogen expression."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

SULT and UGT Genetic Variants Modulate Side Effect Profiles in South African Breast Cancer Patients Treated with Tamoxifen. (PubMed, Genes (Basel)) - "Hot flashes were frequent, affecting 33% of patients, but showed no clear pharmacogenetic associations. This study demonstrates that pharmacogenetic variation is associated with interindividual differences in treatment-related side effects, underscoring the need to expand research in African populations to better inform precision endocrine therapy."

Adverse events • Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Diseases • Oncology • Solid Tumor • CYP3A4 • SULT1A1 • SULT1A2 • SULT1E1 • UGT1A4 • UGT2B15

Estrogen receptor-mediated pharmacogenomic eQTLs as predictors of endocrine therapy response in breast cancer (AACR 2026) - "Here, we mapped ER pharmacogenomic eQTLs to identify germline variants that modulate transcriptional responses to estradiol (E2) and tamoxifen (Tam). We treated 30 genotyped lymphoblastoid cell lines (LCLs) with vehicle, E2, Tam, or E2+Tam and performed RNA-seq to quantify ligand-induced expression fold changes... We identified ligand-dependent ER PGx-eQTLs that mechanistically connect germline regulatory variants to transcriptional response heterogeneity and clinical endocrine therapy outcomes. These SNP-gene relationships represent potential biomarkers for precision endocrine therapy selection and may reveal endocrine-dependent therapeutic vulnerabilities."

Biomarker • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Palazestrant directly recruits the corepressor protein NCoR1 in vitro leading to complete antagonism of estrogen receptor alpha (AACR 2026) - "Contrarily, selective estrogen receptor modulators (SERMs) such as 4-OH-tamoxifen and vepdegestrant either do not induce recruitment or are incomplete recruiters, in line with previous data indicating that SERMs are not complete antagonists...CERAN molecules palazestrant and fulvestrant consistently demonstrate greater suppression of GREB1 and PGR as compared to SERMs in both ESR1 wildtype and mutant ER+ breast cancer models.Functionally, treatment with palazestrant leads to antiproliferative activity in ER+ breast cancer models comparable or superior to investigational and approved anti-estrogens...When cells are not stimulated with E2, SERMs like tamoxifen demonstrate induction of cell proliferation where CERANs do not. Palazestrant is a promising therapeutic strategy for treating ER+/HER2- breast cancer patients and is being evaluated clinically, both as monotherapy and combination."

Preclinical • Breast Cancer • Estrogen Receptor Positive 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 • ER • HER-2 • NCOR1

Functional role of PHLDA1 down regulation leads to morphological changes and increased proliferation in MCF-7 breast cancer cells (AACR 2026) - "Additionally, the obtained clones will be assessed for how PHLDA1 expression influences their response to tamoxifen and fulvestrant treatments. Supported by FAPESP."

Breast Cancer • Oncology • Solid Tumor • PHLDA1 • PLEK

Red cabbage juice reprograms the gut microbiome and enhances butyrate production to prevent colorectal cancer (AACR 2026) - "This study investigated the preventive efficacy of red cabbage juice (RCJ) in a genetically engineered mouse model of CRC by examining its effects on microbial composition, butyrate production and its translational relevance using CRC patient-derived organoids (PDOs).Methods Tamoxifen inducible APCfl/fl; Cdx-CreER (AC) mice for CRC were randomized to receive either phosphate-buffered saline (PBS) or RCJ as oral gavage for 10 weeks...In parallel, PDOs from CRC patients were developed and treated with RCJ alone or in combination with chemotherapeutic agents oxaliplatin or 5-fluorouracil (5-FU) and monitored in real-time on an IncuCyte platform and therapy responses (proliferation and apoptosis) were evaluated by IHC.Results RCJ significantly reduced polyps and tumor progression in AC mice and improved survival compared to PBS group...Notably, RCJ enhances the efficacy of oxaliplatin in PDOs, suggesting its potential to overcome chemoresistance. These findings underscore..."

Colorectal Cancer • Oncology • Solid Tumor • MUC2 • MUC4

Cost-effective targeted DNA mutation and gene expression change profiling in circulating tumor cells using new Droplet Digital PCR technologies (AACR 2026) - "ddPCR is a cost-effective approach for unlocking molecular information carried by CTCs in blood for liquid biopsy. Further studies using clinical specimens with larger sample sizes would facilitate the clinical use of the suggested protocol."

Circulating tumor cells • Cost effectiveness • HEOR • Tumor cell • Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTCs • EGFR • ER • GATA3 • PIK3CA

Epigenetic regulation of histone lysine demethylase 4B on cancer therapy in tamoxifen-sensitive and -resistant breast cancer cells (AACR 2026) - "KDM4B serves as a critical epigenetic regulator in both tamoxifen-sensitive and tamoxifen-resistant ERα-positive breast cancer. Inhibition of KDM4B restores repressive histone marks, suppresses ERα-dependent transcription, and attenuates cellular proliferation and metabolic activity. The heightened dependence of tamoxifen-resistant cells on KDM4B further underscores its potential as a promising therapeutic target for overcoming endocrine therapy resistance."

Epigenetic controller • IO biomarker • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Oncology • Solid Tumor • BCL2 • CCND1 • KDM4B • MYC

Fibroblast-driven tamoxifen resistance in ER+ breast cancer: Experimental validation and development of a high-throughput co-culture screening assay (AACR 2026) - "Tamoxifen at a concentration of 20 µM reduced MCF-7 cell numbers by 63% in monoculture versus 38% in co-culture, confirming the protective stromal effect.In conclusion, our experiments validate fibroblast-ER+ breast cancer crosstalk as a mechanism of tamoxifen resistance. Furthermore, the development of a co-culture-based high-throughput assay, that models fibroblast-mediated tamoxifen resistance, provides a platform for novel screening strategies aimed at targeting the tumor-stroma interactions in ER+ breast cancer."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CCND1 • CD40 • ER • TFF1