VERU-111 as an Oral Tubulin Inhibitor Suppressing Triple-Negative Breast Cancer and Evaluation of Novel Tubulin Inhibitors for Cancer Therapy

Mapping Intimacies ◽

10.21007/etd.cghs.2020.0524 ◽

2020 ◽

Author(s):

◽

Shanshan Deng ◽

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Mortality Rates ◽

Tubulin Inhibitor ◽

Tubulin Inhibitors ◽

Clinical Challenge ◽

Approved Drugs ◽

Fda Approved Drugs

Triple negative breast cancer (TNBC) has aggressive clinical features strongly associated with poorer overall prognosis and higher mortality rates relative to other molecular subtypes. FDA-approved drugs, such as paclitaxel, are effective in treating TNBC. Yet, treatment failure is commonly observed due to the development of acquired chemoresistance, which remains a clinical challenge for TNBC therapy.

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Expression of Transgelin in Triple Negative and Non Triple Negative Breast Cancer: A Differential Study

Tumori Journal ◽

10.1177/0300891620914150 ◽

2020 ◽

Vol 106 (1_suppl) ◽

pp. 20-20

Author(s):

NS Tolba ◽

AS Alsedfy ◽

SW Skandar ◽

YM El-Kerm

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

High Rate ◽

Targeted Treatment ◽

Her2 Status ◽

Altered Expression ◽

Wide Range ◽

Significant Difference

Introduction: Triple negative breast cancer (TNBC) is defined by the absence of ER expression, PR expression and HER2 amplification. No targeted treatment is available for TNBC and chemotherapy remains the best therapeutic option. However, in the case of recurrence or chemo-resistance, therapeutic options are very limited. TNBC presents a high rate of proliferation and is highly aggressive having low survival rate. As the complexity of this disease is being simplified over time, new targets are also being discovered for the treatment of this disease. Therefore, there is still need for new biomarkers, which would serve for targeted treatment. Transgelin was proposed as a new potential cancer biomarker. Altered expression of Transgelin has been described in a wide range of cancers, often with contradictory results. The aim of the study was to compare Transgelin expression across molecular subtypes of breast cancer, to identify if it can be used as a future molecular targeted protein for TNBC. Material and Methods: Transgelin immunohistochemistry was applied on 60 retrospectively collected paraffin blocks of patients presenting with invasive breast carcinoma (NST) having different molecular subtypes. Blocks were collected between 2015 and 2016 from Pathology department, Medical Research Institute, Egypt. Her2 equivocal cases were excluded from the study. Results: Transgelin expression was positive in 23 cases and negative in 37 cases. There was a statistically significant difference between (Transgelin +) and (Transgelin -) cases being highly expressed in TNBC in comparison to other molecular subtypes. It was also highly expressed in tumors with large size, high grade, positive lymph-vascular invasion status & lymph node metastasis. There was no statistically significant difference between (Transgelin+) and (Transgelin-) as regards age and Her2 status. Conclusions: Transgelin is an aggressive biomarker differentially expressed among the molecular breast cancer subtypes with high expression in TNBC. Transgelin may provide a potential target for future treatment of TNBC.

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Abstract 5479: Antitumor effect of KX-01, a novel Src and tubulin inhibitor, in triple negative breast cancer cells

10.1158/1538-7445.am2014-5479 ◽

2014 ◽

Author(s):

Seongyeong Kim ◽

Seock-Ah Im ◽

Ahrum Min ◽

Miso Lee ◽

Heymin Jang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Antitumor Effect ◽

Triple Negative ◽

Tubulin Inhibitor

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High Expression of Trophoblast Cell Surface Antigen 2 in Triple-negative Breast Cancer Identifies a Novel Therapeutic Target

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz113.001 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S37-S37

Author(s):

Elias Makhoul ◽

Farnaz Dadmanesh

Keyword(s):

Breast Cancer ◽

Cell Surface ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Pairwise Comparison ◽

Control Group ◽

Bonferroni Correction ◽

Luminal A ◽

Membranous Staining

Abstract Objectives Patients with triple-negative breast cancer (TNBC) respond poorly to current therapeutic modalities. The newly FDA-approved drug conjugate, Sacituzumab Govitecan, targeting antitrophoblastic cell surface antigen 2 (Trop-2), offers a new modality to treat these subtypes of breast carcinoma (BC). Our study examines expression of Trop-2 by immunohistochemistry (IHC) in TNBC. Methods Forty cases of TNBC were selected from our files (34 ductal, 4 pleomorphic lobular, 1 metaplastic, and 1 mixed ductal and lobular carcinoma). A control group included 11 luminal A-like, 11 luminal B-like, and 8 HER2-like BC. Immunostaining for Trop-2 was performed on 4-micron-thick tissue sections using goat polyclonal antibody (R&D Systems). Three pathologists individually scored the % and intensity of membranous staining. The % of staining was defined as <10%, 10%-50%, and >50%. The intensity of staining was scored as 3+ (crisp circumferential membranous staining), 2+ (medium membranous staining), 1+ (patchy weak membranous staining), and 0 (no staining). A Kruskal-Wallis H-test and pairwise comparison with Bonferroni correction was performed to compare % and intensity of staining in TNBC to control group. Results TNBC exhibited stronger Trop-2 staining in both intensity and extent when compared to the control. The result was significantly different, χ2 (4) = 17.427, P = .001. A pairwise comparison with Bonferroni correction found significant difference between TNBC (42.55) and luminal A (16.65) (P < .001). There was significant agreement (P < .001) among 3 independent pathologists for assessing % and intensity of staining. Conclusion The extent and intensity of staining for Trop-2 is higher in TNBC than in other molecular subtypes of BC. These findings suggest that patients with TNBC may potentially benefit from this targeted therapy. Furthermore, identification of Trop-2 in other molecular subtypes may expand the therapeutic potential of this new drug. Further studies are needed to determine the efficacy of this marker.

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Immune Checkpoint Inhibition for Triple-negative Breast Cancer

Oncology & Hematology Review (US) ◽

10.17925/ohr.2016.12.01.31 ◽

2016 ◽

Vol 12 (01) ◽

pp. 31 ◽

Cited By ~ 1

Author(s):

Poornima Saha ◽

Rita Nanda ◽

◽

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Checkpoint Inhibition ◽

Immune Checkpoint Inhibition ◽

Multiple Tumor ◽

Clinical Challenge ◽

Programmed Death ◽

Programmed Death 1 ◽

Tumor Types

Triple-negative breast cancer remains an important clinical challenge with no targeted therapy available for treatment. Recently, drugs targeting the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) axis have been investigated, with promising responses across multiple tumor types. Two drugs—pembrolizumab and atezolizumab—have recently been explored in advanced triple-negative breast cancer and have demonstrated promising responses.

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