A5023278790- Cancer-related molecular mechanisms research
- Advanced Breast Cancer Therapies
- Peptidase Inhibition and Analysis
- Phosphodiesterase function and regulation
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- RNA modifications and cancer
- Salivary Gland Tumors Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- Histone Deacetylase Inhibitors Research
- HER2/EGFR in Cancer Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Ferroptosis and cancer prognosis
- Colorectal and Anal Carcinomas
- Heat shock proteins research
- Medicinal Plant Pharmacodynamics Research
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Sphingolipid Metabolism and Signaling
- Phagocytosis and Immune Regulation
- Wnt/β-catenin signaling in development and cancer
Beykent University
2023-2025
Bilkent University
2017-2025
Medical Center Hospital
2023
University of South Carolina
2021
Abstract Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as key inducer of chemoresistance by developing chemoresistant TNBC tumors vivo and characterizing their transcriptomes RNA-sequencing. Inhibiting LOX reduces collagen cross-linking fibronectin assembly, increases drug penetration, downregulates ITGA5/FN1 expression, resulting inhibition FAK/Src signaling,...
Abstract Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER + ) breast cancer, constituting around 75% of all cases. However, emergence resistance is common, necessitating identification novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen by blocking tamoxifen-induced ferroptosis, an iron-mediated cell death. Mechanistically, inhibiting reduces mRNA stability...
Breast cancer (BC) is the leading cause of cancer-related mortality among women. The backbone first-line treatment in HR+/HER2+ BC dual anti-HER2 blockade combined with taxane chemotherapy. Although this regimen exhibits high rates response and disease control both HR+ HR− cohorts, some patients could have intrinsic or develop acquired resistance to trastuzumab and/or pertuzumab. Here, we achieved a near-complete HER2 -amplified overexpressing metastatic twice through molecular tumor board...
Abstract Purpose: Tamoxifen remains an important hormonal therapy for ER-positive breast cancer; however, development of resistance is a major obstacle in clinics. Here, we aimed to identify novel mechanisms tamoxifen and provide actionable drug targets overcoming resistance. Experimental Design: Whole-transcriptome sequencing, downstream pathway analysis, repositioning approaches were used modulators [here: phosphodiesterase 4D (PDE4D)] Clinical data involving tamoxifen-treated patients...
Abstract Phosphodiesterase 4D (PDE4D) is a member of the phosphodiesterase family enzymes, catalyzing hydrolysis cAMP second messenger and inhibiting signaling. Targeting PDE4D raises intracellular levels, leading to apoptosis cell cycle arrest in different tumor types. However, its contribution drug resistance metastasis still elusive. lncRNAs are more than 200 nucleotides length carry out diverse functions including transcriptional regulation, regulation proteins or RNA molecules by direct...
ABSTRACT Comprehensive genomic profiling (CGP) and the subsequent discussions in molecular tumor boards (MTBs) are becoming an integral part of personalized cancer care. The patient with metastatic renal cell carcinoma (mRCC) presented here demonstrated absence a favorable response accompanied by adverse events after receiving dual immunotherapy nivolumab plus ipilimumab combination poly (adenosine diphosphate–ribose) polymerase inhibitor, niraparib. This determination was made based on...
Abstract Resistance to endocrine therapy and CDK4/6 inhibitors, the standard of care (SOC) in estrogen receptor-positive (ER+) breast cancer, greatly reduces patient survival. Therefore, elucidating mechanisms sensitivity resistance SOC identifying actionable targets are urgently needed. Here, we show that causes DNA damage toxic PARP1 trapping upon generation a functional BRCAness (i.e., BRCA1/2 deficiency) phenotype, leading increased histone parylation reduced H3K9 acetylation, resulting...
Ewing's sarcoma (ES) is a bone and soft tissue tumor that mainly occurs at young age. The underlying cause of the formation fusion proteins between FET family genes ETS genes. Tumors with FET/ETS can have defects in DNA damage response are sensitive to PARP inhibitors (PARPi). However, several studies shown PARPi alone not sufficient induce meaningful antitumor combinations DNA-damaging agents required achieve efficacy. Accordingly, preclinical reported dramatic responses treatment...
Programmed death ligand 1, PD-L1 (CD274), facilitates immune evasion and exerts pro-survival functions in cancer cells. Here, we report a mechanism whereby internalization of response to alterations bioactive lipid/ceramide metabolism by ceramide synthase 4 (CerS4) induces sonic hedgehog (Shh) transforming growth factor β receptor signaling enhance tumor metastasis triple-negative breast cancers (TNBCs), exhibiting immunotherapy resistance. Mechanistically, data showed that internalized...
There is currently no effective treatment strategy for the recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts unlike non-ACC salivary gland cancers. Genomic profiling revealed actionable targets but NOTCH1 KDM6A frameshift CTCF splice site mutations (no MYB/L fusion) with a low TMB, MSS negative PD-L1. We recommended anti-PD-1 plus anti-CTLA-4 based on TMB 2-fold greater than...
There is currently no effective treatment strategy for recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts, unlike non-ACC salivary gland cancers. Genomic profiling revealed actionable targets but NOTCH1 KDM6A frameshift CTCF splice site mutations (no MYB/L fusion) with a low tumor mutational burden (TMB), microsatellite stable (MSS) negative programmed death ligand 1 (PD-L1) were...
Kinase-impaired class III BRAF mutations have recently received attention as a possible prognostic factor and therapeutic target. Class variants differ from I II in terms of mechanism pathway activation vulnerabilities. Genomic landscape analyses tumors large real-world cohorts represent great opportunity to further characterize tumor-related molecular events treatment vulnerabilities, however, such data is not yet available for with mutations.
Breast cancer (BC) is the leading cause of cancer-related mortality among women, and hormone receptor (HR)-positive subtype makes up majority all cases. The standard care in HR + /HER2 − metastatic BC (MBC) endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i). ESR1 mutations could impair clinical efficacy ETs. Similarly, PIK3CA may serve as negative prognostic marker. Furthermore, MBC challenging to treat despite new drug approvals. Our patient received multiple lines ET ± CDK4/6i...
Complete response to Trametinib in a heavily-pretreated sarcoma: RAF1 as predictor of MEKi Response
Abstract Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER+) breast cancer, constituting around 75% of all cases. However, emergence resistance is common, necessitating identification novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen via blocking tamoxifen-induced ferroptosis, an iron-mediated cell death. Mechanistically, inhibiting reduces mRNA stability phosphodiesterase...
Abstract Estrogen receptor (ER)-positive (ER+) breast cancer has the highest incidence rate and accounts for around 75% of all cases. Endocrine therapy CDK4/6 inhibitors are standard care (SOC) in ER+ cancer; however, resistance is common, it greatly reduces patient survival. Therefore, elucidating mechanisms sensitivity to SOC identifying actionable targets urgently needed. Here, we show that causes DNA damage toxic PARP1 trapping upon generation a functional BRCAness (i.e., BRCA1/2...
Abstract Endocrine therapies, modulating ER level and/or activity, and the CDK4/6 inhibitors are among standard-of-care (SOC) therapies used in estrogen receptor-positive (ER+) breast cancer. However, most ER+ cancer patients eventually develop resistance to SOC, representing a major clinical challenge that reduces outcome. Therefore, elucidating common mechanisms of sensitivity SOC identifying novel actionable targets urgently needed. Here, we demonstrated cell death induced by endocrine...
This paper presents a patient with novel Ig-like-III domain fibroblast growth factor receptor (FGFR2) alteration (W290_P307>C) along CDKN2A/B alterations and cadherin 1 (CDH1) alteration. Initial responsiveness to pazopanib monotherapy was encouraging, yet progression occurred after 7.5 months. Following progression, the molecular tumor board recommended combination therapy approach comprising pazopanib, crizotinib, palbociclib target all of changed pathways at same time. Pazopanib chosen...
Metastatic colon adenocarcinoma presents significant challenges in treatment, particularly when resistant to standard therapies. Precision oncology, guided by multidisciplinary tumor boards (MTBs), offers a promising way for individualized therapeutic approaches. Integration of comprehensive genomic profiling (CGP) and minimal residual disease (MRD) testing strengthens treatment decision-making, yet persist identifying overcoming resistance mechanisms. FLT3 amplification can be one those...