- |||||||||| Xuan Yue Ning (bireociclib) / Sihuan Pharmaceutical
Dynamic monitoring and identification of reliable biomarkers to predict efficacy of bireociclib and fulvestrant: An exploratory ctDNA analysis of the BRIGHT-2 study (Section 36) - Mar 17, 2026 - Abstract #AACR2026AACR_10024;
P3
Dynamic clearance of ctDNA or specific gene mutations was correlated with improved efficacy and survival outcomes for CDK4/6 inhibitor.Conclusions Both baseline and dynamic monitoring of ctDNA demonstrated salient predictive value for treatment response and survival outcomes in hormone receptor-positive, HER2-negative breast cancer patients receiving bireociclib plus fulvestrant. These potential biomarkers warrant further validation through larger clinical trials and basic researches.Key words: CDK4/6 inhibitor, advanced breast cancer, biomarkers, bireociclib, prognosis.
- |||||||||| fulvestrant / Generic mfg.
A first-in-class orally bioavailable small molecule to overcome treatment resistance in hormone receptor-positive breast cancer (Section 14) - Mar 17, 2026 - Abstract #AACR2026AACR_9977;
CDK4/6 inhibitors combined with antiestrogens such as fulvestrant represent frontline therapy for hormone receptor-positive (HR+) breast cancer; however, therapeutic resistance inevitably emerges in a substantial subset of patients through diverse molecular mechanisms...In preclinical HR+ breast cancer xenograft models, PMG-A9 exhibits robust single-agent antitumor activity and pronounced synergy when combined with these agents. These findings highlight tumor-suppressor reactivation as a promising and broadly applicable therapeutic strategy with the potential to address resistance not only in HR+ breast cancer but also across a wide range of tumor types.
- |||||||||| LY4257496 / Eli Lilly
Characterization of LY4257496, a novel GRPR antagonist radiolabeled with lutetium-177 (Section 17) - Mar 17, 2026 - Abstract #AACR2026AACR_9835;
P1
In biodistribution analyses, LY4257496 exhibited favorable pharmacokinetics with rapid tumor targeting and prolonged retention (% ID/g 22.6 at 1h, 11.6 at 24h), fast clearance from normal organs (all tissues below 3.5 % ID/g at 24h), and > 50% renal excretion. LY4257496 was well tolerated at 10, 20 and 30MBq (Q14DX2), and efficacy was dose dependent in T47D xenografts (26, 72, and 72 % TGI, respectively).
- |||||||||| fulvestrant / Generic mfg.
Patient-derived models of primary breast cancer for preclinical evaluation of neoadjuvant therapies (Section 26) - Mar 17, 2026 - Abstract #AACR2026AACR_9009;
For triple-negative IBC, we demonstrate that neoadjuvant treatment does not benefit from addition of a PARP inhibitor, while for estrogen receptor (ER) positive IBC the combination of a CDK4/6 inhibitor and fulvestrant improves neoadjuvant treatment response. Our work provides a valuable resource of primary IBC models to study breast cancer biology and develop novel neoadjuvant treatments.
- |||||||||| fulvestrant / Generic mfg.
Discovery of an orally bioavailable AKT degrader with sustained in vivo efficacy and translational potential (Section 15) - Mar 17, 2026 - Abstract #AACR2026AACR_8600;
DWP221/PIN002 was well tolerated throughout the study period, without notable body-weight loss or overt signs of systemic toxicity, and maintained a favorable exposure-response relationship consistent with its drug-like properties.This study demonstrates that an orally bioavailable AKT degrader can achieve durable target suppression and in vivo efficacy through sustained exposure and efficient target engagement. These findings support that targeted protein degradation may overcome key limitations of conventional kinase inhibition and provide a differentiated approach toward next-generation targeted therapies for PI3K-AKT-driven cancers.
- |||||||||| Ibrance (palbociclib) / Pfizer, KC1086 / Konruns Pharma, prifetrastat (PF-07248144) / Pfizer
A highly selective KAT6/7 dual inhibitor with best-in-class potential and favorable pharmacokinetic profile (Section 14) - Mar 17, 2026 - Abstract #AACR2026AACR_7137;
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 supported clinical development of KC1086 as a dual KAT6/7 inhibitor with best-in-class potential.
- |||||||||| Kisqali (ribociclib) / Novartis
Shifting the gut microbiome to alleviate anti-cancer treatment-induced cardiovascular toxicity (Section 41) - Mar 17, 2026 - Abstract #AACR2026AACR_7056;
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. Mice were randomized by tumor volume into treatment groups: untreated control, probiotics (Probx; 2
- |||||||||| fulvestrant / Generic mfg.
Transcriptomic analysis of small extracellular vesicles in metastatic breast cancer (Section 45) - Mar 17, 2026 - Abstract #AACR2026AACR_6728;
We demonstrate a workflow for isolating sEV-RNAs from plasma for RNA sequencing. We used sensitive MCF7 and fulvestrant-resistant MCF7 (FULVR-MCF7) breast cancer cell lines to optimise a workflow that combines ExoGAG technology for EV isolation with the Ion AmpliSeq
- |||||||||| palazestrant (OP-1250) / Olema Pharma
Palazestrant directly recruits the corepressor protein NCoR1 in vitro leading to complete antagonism of estrogen receptor alpha (Section 11) - Mar 17, 2026 - Abstract #AACR2026AACR_5850;
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.
- |||||||||| Fablyn (lasofoxifene) / Sermonix
Lasofoxifene is a bone protective treatment option for estrogen receptor positive breast cancers (Section 32) - Mar 17, 2026 - Abstract #AACR2026AACR_4803;
P3
Lasofoxifene, a selective ER modulator, exhibits tissue-selective ER-agonist activity in bone and is currently being evaluated in the ELAINE-III clinical trial [NCT05696626] in combination with abemaciclib for the treatment of ESR1-mutant advanced or metastatic ER+ breast cancer...Drug synergy screens have defined choices for rational combination with lasofoxifene to further potentiate its anti-tumor activity. Overall, this study supports the use of lasofoxifene-based treatment combinations which will concurrently protect bone architecture while suppressing ER+ metastasis progression in the bone niche.
- |||||||||| tamoxifen / Generic mfg., fulvestrant / Generic mfg.
Targeting succinate dehydrogenase impairs the proliferation of ER+ breast cancer cells (Section 16) - Mar 17, 2026 - Abstract #AACR2026AACR_4555;
Taken together, SDH enzymatic activity is crucial for the proliferation and mitochondrial function of ET-resistant ER+ breast cancer cells. We propose that SDH is a potentially novel therapeutic target for ER+, endocrine therapy resistant breast cancer.
- |||||||||| Mekinist (trametinib) / Novartis, BeOne Medicines
ELF3-driven epigenetic reprogramming creates ERK pathway dependency in SERD-resistant ER+ breast cancer (Section 16) - Mar 17, 2026 - Abstract #AACR2026AACR_4548;
Selective estrogen receptor degraders (SERDs) such as fulvestrant represent a promising therapeutic strategy for endocrine-resistant ER+ breast cancers...Experimental validation showed that resistant cells exhibited marked ERK pathway activation and developed strong dependency on ERK signaling, with increased sensitivity to MEK inhibitor trametinib...We define a novel mechanism of SERD resistance where the ERlow/ELF3hi state drives resistance by activating an ELF3-ERK signaling axis. Targeting this pathway may overcome resistance in ERlow/ELF3hi tumors.
- |||||||||| Orserdu (elacestrant) / Menarini, Inluriyo (imlunestrant) / Eli Lilly
Targeting estrogen receptor mutations and aberrant myelopoiesis in hormone resistant breast cancer (Section 34) - Mar 17, 2026 - Abstract #AACR2026AACR_4336;
Until recently, fulvestrant was the only selective estrogen receptor degrader (SERD) available to counteract endocrine resistance; however, two next-generation SERDs, elacestrant and imlunestrant, have now received FDA approval...Furthermore, combining endocrine agents with immunotherapy may help mitigate immune suppressive myeloid populations within the TME and enhance T-cell-mediated anti-tumor responses. Funding: CIRM DISC2-14166, UCLA JCCC BC Award, Tower Cancer Res Found, Hickey Foundation, NIH/NCI U54 CA143930 CDU-UCLA JCCC Partnership, CBCRPB27IB3869, DOD BCRPBC181420.
- |||||||||| Ibrance (palbociclib) / Pfizer, Orserdu (elacestrant) / Menarini, Inluriyo (imlunestrant) / Eli Lilly
AZD4241, an orally bioavailable ER? PROTAC, degrades wild-type and mutant ER? and delivers anti-tumour activity in preclinical breast cancer models (Section 34) - Mar 17, 2026 - Abstract #AACR2026AACR_4335;
Current ER?pathway inhibitors include aromatase inhibitors (letrozole, anastrozole, exemestane), selective estrogen receptor modulators (SERMs; tamoxifen), and selective estrogen receptor degraders (SERDs; fulvestrant, elacestrant, imlunestrant)...In vivo, AZD4241 induced dose?dependent anti?tumour activity and, in some cases, tumour regressions across ESR1wt and ESR1m patient?derived xenograft (PDX) models, including a palbociclib?resistant model...Collectively, these data confirm that AZD4241 is a potent, orally bioavailable degrader of wt and mutant ER?, driving anti-tumour efficacy in ESR1wt, ESR1m, and CDK4/6 inhibitor?resistant PDX models. These findings support the use of AZD4241 as a novel ER-PROTAC with potential to overcome key resistance mechanisms to current standards of care and deliver clinical benefit for patients with ER?positive breast cancer.
- |||||||||| fulvestrant / Generic mfg.
DNA methylation-based classifier predicts SERD benefit in ESR1 wild-type HR+/HER2- breast cancer (Section 34) - Mar 17, 2026 - Abstract #AACR2026AACR_4333;
This classifier enables real-time, noninvasive stratification of ESR1-wt patients, identifying a molecularly defined subset more likely to derive benefit from SERD-based therapy. These findings support the potential clinical utility of methylation-based biomarkers to extend precision endocrine therapy beyond ESR1 mutation profiling.
- |||||||||| OncoKB (Section 43) - Mar 17, 2026 - Abstract #AACR2026AACR_4152;
These findings support the potential clinical utility of methylation-based biomarkers to extend precision endocrine therapy beyond ESR1 mutation profiling. To date OncoKB
- |||||||||| alisertib (MLN8237) / Puma
Therapeutic potential of AURKA inhibition in ER+ inflammatory breast cancer (Section 18) - Mar 17, 2026 - Abstract #AACR2026AACR_3423;
In ER+ IBC AURKA amplification is inversely correlated with putative synthetic lethal partner SMARCA4. We have characterized IBC models with high AURKA expression and demonstrated sensitivity to AURKA inhibition with fulvestrant.
- |||||||||| onvansertib (PCM-075) / Cardiff Oncology, Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
PLK1 inhibitor onvansertib potentiates the antitumor efficacy of trastuzumab deruxtecan (T-DXd) and reverses its resistance in therapy-resistant HER2-low breast cancer models (Section 14) - Mar 17, 2026 - Abstract #AACR2026AACR_3333;
Onvansertib, a selective polo-like kinase 1 inhibitor, has shown clinical benefit in combination with the TOP1i irinotecan in metastatic colorectal cancer...The HR+ PDXs originated from primary or metastatic tumors and were resistant to fulvestrant and/or CDK4/6 inhibitors...Taken together, our data indicate that onvansertib enhances T-DXd's antitumor activity and overcomes resistance through synergistic induction of DNA damage and apoptosis. The findings support the clinical potential of this combination for advanced HER2-low breast cancer resistant to standard-of-care therapies.
- |||||||||| Ibrance (palbociclib) / Pfizer
Development of a novel selective CDK4 inhibitor for HR+/HER2- breast cancer (Section 49) - Mar 17, 2026 - Abstract #AACR2026AACR_3209;
Preliminary in vitro combination studies revealed that pairing the selective CDK4 inhibitor with a CDK2 inhibitor or a PI3K inhibitor produced significant synergistic inhibitory effects on MCF7 and palbociclib-resistant MCF7 cells. Optimization of the lead compound is ongoing with the goal of identifying a preclinical candidate (PCC) for IND-enabling studies.# Apeng Liang and Meihua Li contributed equally to this work.* Correspondence authors.
- |||||||||| Lytgobi (futibatinib) / Otsuka
Trial completion date, Trial primary completion date, Monotherapy: Futibatinib in Patients Previously Enrolled in an Antecedent Futibatinib as Monotherapy or Combination Therapy. (clinicaltrials.gov) - Mar 11, 2026
P2/3, N=15, Enrolling by invitation,
An accurate annotation of ER isoforms will aid in interpretation of clinical data and inform functional studies to improve our understanding of the ER in health and disease. Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: Dec 2026 --> Apr 2027
- |||||||||| sirolimus / Generic mfg., pioglitazone / Generic mfg., fulvestrant / Generic mfg.
Journal: Computational discovery of precision therapeutics for hidradenitis suppurativa. (Pubmed Central) - Mar 9, 2026
These results show that unbiased data-driven precision medicine approaches can identify novel therapies for HS and can serve more generally as a model approach for therapeutic discovery in other chronic inflammatory diseases. Data-driven precision medicine approach identifies sirolimus, pioglitazone, and fulvestrant as novel therapies for hidradenitis suppurativa.
- |||||||||| fulvestrant / Generic mfg., Verzenio (abemaciclib) / Eli Lilly
Journal: Vulvar Metastasis from Breast Cancer Treated with Abemaciclib plus Fulvestrant: A Case Report. (Pubmed Central) - Mar 4, 2026
To the best of our knowledge, this is the first reported case of vulvar metastasis from breast cancer that was successfully treated with the combination of abemaciclib and fulvestrant, leading to a complete response. The use of CDK4/6 inhibitors for the treatment of vulvar metastases of breast origin represents a significant advance, offering a less invasive and potentially more effective alternative to current treatment protocols.
- |||||||||| MRT-2359 / Monte Rosa Therap
Enrollment closed: MRT-2359-001: Study of Oral MRT-2359 in Selected Cancer Patients (clinicaltrials.gov) - Mar 3, 2026
P1/2, N=174, Active, not recruiting,
The use of CDK4/6 inhibitors for the treatment of vulvar metastases of breast origin represents a significant advance, offering a less invasive and potentially more effective alternative to current treatment protocols. Recruiting --> Active, not recruiting
- |||||||||| Piqray (alpelisib) / Novartis
Enrollment closed, Trial completion date, Trial primary completion date: GOG-3069: A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer (clinicaltrials.gov) - Mar 3, 2026
P2, N=51, Active, not recruiting,
Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting | Trial completion date: Apr 2026 --> Nov 2028 | Trial primary completion date: Apr 2025 --> May 2028
- |||||||||| Piqray (alpelisib) / Novartis, tamoxifen / Generic mfg., fulvestrant / Generic mfg.
Preclinical, Journal: Targeting Semaphorin 7a signaling in preclinical models of endocrine therapy-resistant breast cancer. (Pubmed Central) - Mar 3, 2026
Combination of an anti-SEMA7A antibody (SmAbH1) (100-250 ug/100uL, every other day) and fulvestrant (83 mg/kg, every 5 days) also revealed that direct inhibition of SEMA7A via SmAbH1 significantly reduces tumor growth of SEMA7A-expressing tumors, and that the efficacy of SmAbH1 is not diminished by the standard of care, fulvestrant. Overall, our studies suggest that patients with ER+SEMA7A+ tumors should be candidates for PI3K-targeted therapies or anti-SEMA7A-based therapy.
- |||||||||| Piqray (alpelisib) / Novartis, Truqap (capivasertib) / AstraZeneca
Case Report of Tumour Response to Capivasertib after Exposure to Alpelisib (Poster Room | Pacifico Yokohama Exhibition Hall D) - Mar 2, 2026 - Abstract #JSMO2026JSMO_2441;
In February 25, she developed intracranial metastasis and underwent stereotactic radiosurgery before initiating fulvestrant and capivasertib at 400mg twice daily for 4 days then 3 days off. Imaging after 3 months of treatment showed good partial response in the liver and stable disease in the lungs and bone.
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