A5090348690- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Cancer Treatment and Pharmacology
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- Radiation Effects and Dosimetry
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- Skin Protection and Aging
- Radiopharmaceutical Chemistry and Applications
- RNA Research and Splicing
- Breast Cancer Treatment Studies
- Insect and Pesticide Research
- Molecular Biology Techniques and Applications
- Effects of Radiation Exposure
- Transgenic Plants and Applications
- Plant Virus Research Studies
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Genomics, phytochemicals, and oxidative stress
- Bacterial Genetics and Biotechnology
Indiana University – Purdue University Indianapolis
2015-2018
Indiana University School of Medicine
2015-2018
University of West Florida
1995
As CDK4/6 inhibitor (CDK4/6i) approval changed treatment strategies for patients with hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer (BC), understanding how exposure to CDK4/6i affects the tumor genomic landscape is critical precision oncology. Using real-world data (RWD) profiling from 5910 metastatic HR+/HER2- BC, we investigated evolution of alteration prevalence in commonly mutated genes across patient journeys. We found that ESR1 more often altered tumors exposed at...
We have developed very efficient suicide functions for biological containment based on the lethal Escherichia coli relF gene. The are placed in duplicate within a plasmid and arranged to prevent inactivation by deletion, recombination, insertional inactivation. efficiency of this concept was tested system that prevents transfer plasmids wild-type bacteria. Protection against assayed test tubes rat intestine. refractory mutation transposons. also soil seawater. show unprecedented can be...
Abstract Purpose: GDC-0927 is a novel, potent, nonsteroidal, orally bioavailable, selective estrogen receptor (ER) degrader that induces tumor regression in ER+ breast cancer xenograft models. Patients and Methods: This phase I dose-escalation multicenter study enrolled postmenopausal women with ER+/HER2− metastatic to determine the safety, pharmacokinetics, recommended II dose of GDC-0927. Pharmacodynamics was assessed [18F]-fluoroestradiol (FES) PET scans. Results: Forty-two patients...
1061 Background: Limitations of current approved endocrine therapies (ETs), a mainstay tx for ER+ BC, include incomplete ER signaling inhibition. Novel ETs, such as selective estrogen receptor antagonists and degraders (SERDs), may help overcome this. G, potent, nonsteroidal, oral (PO) SERD, is well tolerated has shown robust occupancy encouraging antitumor activity monotherapy in combination with the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib (P). MORPHEUS BC (NCT04802759)...
In response to sublethal ultraviolet B (UVB) irradiation, human keratinocytes transiently block progression of the cell cycle allow ample time for DNA repair and fate determination. These cellular activities are important avoiding initiation carcinogenesis in skin. Central these processes is repression mRNA translation through GCN2 phosphorylation eIF2α (eIF2α-P). Concurrent with reduced global protein synthesis, eIF2α-P accompanying integrated stress (ISR) selectively enhance mRNAs involved...
Abstract BACKGROUND Patients with estrogen receptor-positive metastatic breast cancer (ER+ mBC) almost always progress on first-line endocrine therapy (ET), which is usually combined a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Finding effective ET combinations after progression following CDK4/6is remains challenge. Giredestrant (GIR) highly potent, nonsteroidal, oral, selective ER antagonist and degrader. Inavolisib (INAVO) potent PI3Kα-selective that promotes degradation of mutated...
Abstract BACKGROUND Giredestrant (GIR) is a highly potent, oral, selective estrogen receptor antagonist and degrader (SERD) that exhibits robust (ER) occupancy. The Phase II, randomized, open-label acelERA Breast Cancer (BC) study (NCT04576455) assessed GIR vs physician’s choice of endocrine therapy (PCET) in second- or third-line ER-positive, HER2-negative advanced BC (ER+, HER2– aBC). did not reach statistical significance for the primary endpoint investigator-assessed progression-free...
<p>Supplementary Tables S1, S2, and S3.</p>
<p>Supplementary Fig. S4. ESR1 mutation analysis in ctDNA.</p>
<p>Supplementary Fig. S3. Clinical benefit does not correlate with ctDNA ESR1 mutant allele frequency (MAF) baseline levels or dynamics upon treatment, ER and PR protein by IHC in tumor tissue.</p>
<p>Supplementary Fig. S2. The PGR z-score for six patients analyzed in 4.</p>
<p>Supplementary Fig. S1. Study scheme.</p>
<div>Abstract<p>Background: GDC-0927 is a novel, potent, non-steroidal, orally bioavailable, selective estrogen receptor (ER) degrader (SERD) that induces tumor regression in ER+ breast cancer xenograft models. Methods: This phase I dose-escalation multicenter study enrolled postmenopausal women with ER+/HER2- metastatic to determine the safety, pharmacokinetics, and recommended II dose of GDC-0927. Pharmacodynamics was assessed [<sup>18</sup>F]-fluoroestradiol (FES)...
<p>Supplementary Fig. S6. Detection of short variant gene alterations using the FACT next generation sequencing assay on ctDNA samples from patients dosed at 1400 mg dose (n=23).</p>
<p>Supplementary Fig. S5. Kaplan-Meier estimate of progression-free survival for patients with and without ESR1 mutations in baseline ctDNA samples collected from the 1400 mg dose group. data was available 36 dosed at mg.</p>
<p>Supplementary Fig. S5. Kaplan-Meier estimate of progression-free survival for patients with and without ESR1 mutations in baseline ctDNA samples collected from the 1400 mg dose group. data was available 36 dosed at mg.</p>
<p>Supplementary Fig. S6. Detection of short variant gene alterations using the FACT next generation sequencing assay on ctDNA samples from patients dosed at 1400 mg dose (n=23).</p>
<p>Supplementary Tables S1, S2, and S3.</p>
<p>Supplementary Fig. S1. Study scheme.</p>
<p>Supplementary Fig. S2. The PGR z-score for six patients analyzed in 4.</p>
<p>Supplementary Fig. S4. ESR1 mutation analysis in ctDNA.</p>
<p>Supplementary Fig. S3. Clinical benefit does not correlate with ctDNA ESR1 mutant allele frequency (MAF) baseline levels or dynamics upon treatment, ER and PR protein by IHC in tumor tissue.</p>