Development of better cancer drugs
Cancers arise from genetically abnormal cells that undergo uncontrolled proliferation or improper differentiation and evade the body's control mechanisms that normally eliminate defective cells. A significant challenge for developing cancer therapies is identifying targets that are expressed only by the tumor cells and not by normal cells such that targeted therapies can be developed. Another challenge is that many cancers are highly unstable genetically and contain many heterogeneous subclones that may respond differently to treatments. If a treatment does not eliminate all the proliferative subclones of the tumor, resistant cells may emerge leading to tumor recurrence. Conventional tumor therapy involves a combination of surgery, chemotherapy and targeted radiation therapy. Chemotherapy agents are non-selective and target all proliferating cells indiscriminately and therefore have considerable side effects. There are numerous novel therapeutic strategies being explored including: the use of specific monoclonal antibodies, utilizing the patient's own immune system to identify and attack tumor cells, small molecules that target specific proteins used by the tumor for growth, migration or angiogenesis, and treatments that promote differentiation of tumor cells to normal functional cells. There is a need for better in vitro cell models of cancer that represent the genetic diversity of primary human tumors and model the development of drug resistance such that better therapies can be developed to treat cancers and prevent cancer recurrence.
Primary cancer cells and tissue
Most primary tumours contain multiple subclones and have genetic heterogeneity since one of the hallmarks of cancer is genome instability. The majority of
cancer cell lines are propagated through hundreds of passages and as a result a single clone dominates the culture and the genetic heterogeneity of the
primary tumor is lost. Therefore, primary tumor cells and tissues are an extremely valuable resource for understanding the biology of human tumors and how
tumors respond to therapies.
Through Axol's custom cell and tissue sourcing service, we can access fresh frozen or formalin-fixed, paraffin-embedded primary human tumor tissue from fully informed consenting donors. We can supply primary tissue for a wide range of cancers including the following:
- Adrenal Cancers
- Bladder Cancers
- Breast Ductal Carcinoma In Situ
- Breast Cancers
- Breast Cancer Tamoxifen Treated
- Cervical Cancers
- Colorectal Cancers
- Esophageal Cancers
- Gall Bladder Cancers
- Head and Neck Cancers
- Lung Cancers
- Ovarian Cancers
- Pancreatic Cancers
- Prostate Cancers
- Renal Cancers
- Skin Cancers
- Spleen Cancers
- Stomach Cancers
- Testicular Cancers
- Thyroid Cancers
- Uterine Cancers
Custom cell & tissue sourcing
Custom cell sourcing
Breast cancer cell lines
The estrogen receptor (ER)-positive breast cancer cell line, MCF7, was treated with the ER targeting drugs tamoxifen or fulvestrant long term and resistant clones
were propagated further. The resulting cell lines are available together with the parental, drug sensitive MCF7 cell line. All of the MCF7 cell lines can be
cultured in low serum (1%) conditions to reduce estrogen exposure from fetal bovine serum. The cell lines permit studies into ER signaling and mechanisms of
resistance to drugs that target the estrogen receptor.
Tamoxifen and fulvestrant block estrogen signaling by interacting with ER and so they are commonly used to treat ER+ breast cancers. Metabolized tamoxifen binds to ER and inactivates it leading to downregulation of pathways that promote proliferation in breast tissue. In other tissues such as endometrium, however, tamoxifen partially activates ER signaling. By contrast, fulvestrant binds to ER and subsequently leads to degradation of ER, meaning it blocks the activity of ER completely and stops proliferation of cells that are normally responsive to estrogen.
Click on the products to find out more and to see the publications where these lines have been used to discover new insights into estrogen receptor signaling and resistance mechanisms.