Breast cancer is the most frequent malignancy in women, contributing to 11.7% of all new cancer cases and 6.8% of all cancer-related deaths worldwide in 2020. Whilst medical interventions and diagnoses are a major focus of the breast cancer field, extensive research surrounding the inherent biology of breast cancer remains ongoing.
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Receptors | |||
---|---|---|---|
Subtype | Estrogen | Progesterone | HER2 |
Luminal A | + | + | - |
Luminal B | + | + | + |
HER2+ | - | - | + |
TBNC | - | - | - |
The genomics of breast cancers have been thoroughly dissected revealing the heterogeneity in driver mutations. Studies have identified further subtypes within HER2+ and TNBC tumors, allowing stratification of these tumors and more refined treatment options. Inhibition of distinct pathways can be used in research to mimic treatment and show how tumor sub-populations adapt and respond. For example, Lapatinib (Cat. No. 6811), a HER-2 inhibitor, and Avagacestat (Cat. No. 6363), a γ-secretase inhibitor, have been used to explore the dynamics of HER2 heterogenous tumor populations and the resulting tumor response and adaptation. Another strategy uses targeted protein degradation to knockdown specific proteins in cells. For example, the PROTAC® Degrader SJF 1528 (Cat. No. 7262) degrades HER2 and EGFR and can be used to understand cancer pathways and responses to the degradation of these proteins.
Histological subtype | Ductal | Lobular |
---|---|---|
Preinvasive (25%) Cells are limited to the basement membrane | Ductal carcinoma in situ Likely to spread through ducts and cause distortion of structure Tends to be unilateral Small proportion progress to invasive | Lobular carcinoma in situ No distortion of duct structure Genetic E-cadherin loss Can be bilateral |
Invasive (75%) Cells extend beyond the basement membrane | Invasive ductal carcinoma Usually progression from ductal carcinoma Fibrous, palpable mass Lymph and blood metastasis | Invasive lobular carcinoma Metastasis to GI, ovaries, uterus Less fibrosis or palpable mass Usually ER+ |
RNA in-situ hybridization (ISH) approaches are increasingly being applied to improve subtype characterization and to direct therapeutic selection. RNAscope™ is an example of this technique, allowing for biomarker identification, tumor subtyping and expression analysis, in addition to many other research applications. For example, RNA probes for EGFR and ERBB2 could be used to understand the transcriptional changes and responses within a cancer cell to treatment with Lapatinib. Combining these RNA-based assays with compound screens can also be a way to identify new genes, drugs of interest, or novel drug effects.
Despite the enormous heterogeneity, there are some genetic changes that are characteristic amongst several breast cancers and between different subtypes. Some of the most frequently mutated genes include oncogenic/hyper activation of PIK3CA, MAP2K4 and KMT2C, and loss of tumor suppressors such as TP53 and PTEN. BRCA1/2 mutations and their role in the increased familial risk of breast cancer is well established; mutations in BRCA1/2 and other DNA damage response (DDR) genes are frequently observed at later stages of breast cancer tumorigenesis. As a result of this, BRCA-deficient cells are reliant on other DNA repair pathways that can create therapeutic vulnerabilities, for example the RAD52 inhibitor 6-Hydroxy-DL-DOPA (Cat. No. 5740) inhibits proliferation in BRCA-deficient cells.
The ability of cancer cells to adapt and evolve is a key to therapeutic resistance and relapse. For example, inhibition of poly(ADP-ribose) polymerase (PARP) by Veliparib (Cat. No. 7026) is effective in treating tumors but resistance can develop. Using cell culture or breast tumor organoids, an understanding of the mechanisms of resistance to Veliparib and the adaptive use of other pathways could be gained. Drug combinations and synthetic lethality can also be studied in this way. For example Trastuzumab and Iressa (Cat. No. 3000) are known synergistic drug combinations, effectively inhibiting breast cancer cells across several subtypes.
PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.
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Target | Top Products | New Products |
---|---|---|
ALK | A-83-01, SB 216763 | TL 13-12, TL-13-112 |
mTOR | Torin 1, Torin 2 | |
AURKB | ZM 447439, TC-A 2317 | |
CTNNB1 | XAV 939 (available sythesized to cGMP guidelines), iCRT 14 | xSTAx-VHLL |
BRAF | SB 590885 | CG 858 |
MET | PHA 665752 | |
HSP90 | VER 155008 | |
MDM2 | SP 141, Nutlin 3a | |
SRC | A 419259 | ND1-YL2 |
Wnt | PKF 115584 (Calphostin C), FH 535 | |
MYC | KJ Pyr 9 | |
CDK4/6 | BSJ-03-204, Ribociclib | BSJ-04-132 |
RAR | BMS 753 | |
PIK3CB | LY 294002 hydrochloride, Wortmannin | |
MEK1 | SL 327 | |
FOXM1 | RCM 1 | |
BRD4 | (+)-JQ1, MZ 1 | |
STAT3 | Stattic, NSC 74859 | HJC 0416 |
ESR1 | ICI 182,780, G-1 | |
FOXA1 | (+)-JQ1 | |
PARP | SK 575, Olaparib | |
Bcl-xL | A 1331852 | |
ErbB2/HER2 | Tucatinib | |
LMTK3 | C28 |
Tocris offers the following scientific literature for Breast Cancer to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
This product guide provides a review of the cell cycle and DNA damage research area and lists over 170 products, including research tools for:
This brochure highlights the tools and services available from Bio-Techne to support Targeted Protein Degradation research, including:
Written by Susanne Müller-Knapp and Peter J. Brown, this review gives an overview of the development of chemical probes for epigenetic targets, as well as the impact of these tool compounds being made available to the scientific community. In addition, their biological effects are also discussed. Epigenetic compounds available from Tocris are listed.
Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.
Produced by Tocris and updated in 2014, the epigenetics research bulletin gives an introduction into mechanisms of epigenetic regulation, and highlights key Tocris products for epigenetics targets including:
This poster summarizes the main metabolic pathways in cancer cells and highlights potential targets for cancer therapeutics. Genetic changes and epigenetic modifications in cancer cells alter the regulation of cellular metabolic pathways providing potential cancer therapeutic targets.
In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.
Adapted from the 2015 Cancer Product Guide Edition 3, this poster summarizes the main epigenetic targets in cancer. The dysregulation of epigenetic modifications has been shown to result in oncogenesis and cancer progression. Unlike genetic mutations, epigenetic alterations are considered to be reversible and thus make promising therapeutic targets.
Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.