Estrogen Receptor In Cancer Cells Research Articles

Light-Activating PROTACs in Cancer: Chemical Design, Challenges, and Applications

Nonselective cell damage remains a significant limitation of radiation therapies in cancer. Decades of successful integration of radiation therapies with other medicinal chemistry strategies significantly improved therapeutic benefits in cancer. Advancing in such technologies also led to the development of specific photopharmcology-based approaches that improved the cancer cell selectivity and provided researchers with spatiotemporal control over the degradation of highly expressed proteins in cancer (proteolysis targeting chimeras, PROTACs) using a monochrome wavelength light source. Two specific strategies that have achieved notable successes are photocage and photoswitchable PROTACs. Photocaged PROTACs require a photolabile protecting group (PPG) that, when radiated with a specific wavelength of light, irreversibly release PPG and induce protein degradation. Thus far, diethylamino coumarin for estrogen-related receptor α (ERRα), nitropiperonyloxymethyl (BRD4 bromodomain protein), and 4,5-dimethoxy-2-nitrobenzyl for (BRD4 bromodomain protein, as well as BTK kinase protein) were successfully incorporated in photocaged PROTACs. On the other hand, photoswitches of photoswitchable PROTACs act as an actual ON/OFF switch to target specific protein degradation in cancer. The ON/OFF function of photoswitches in PROTACs (as photoswitchable PROTACs) provide spatiotemporal control over protein degradation, and to an extent are correlated with their photoisomeric state (cis/trans-configuration), showcasing an application of the photochemistry concept in precision medicine. This study compiles the photoswitchable PROTACs targeted to bromodomain proteins: BRD 2, 3, and 4; kinases (BCR-ABL fusion protein, ABL); and the immunophilin FKBP12. Photocaging of PROTACs found successes in selective light-controlled degradation of kinase proteins, bromodomain-containing proteins, and estrogen receptors in cancer cells.

Anastrozole as aromatase inhibitor – new approaches to breast cancer treatment in postmenopausal women

Introduction. Anastrozole is a chemotherapeutic drug used to treat breast cancer in postmenopausal women. The condition for success of this type of treatment is the presence of estrogen receptors in cancer cells. Anastrozole belongs to strong-acting, nonsteroidal inhibitors of aromatase, which is responsible for androgen-estrogen conversion process. The metabolism of this drug is based on biotransformation both in phase I and II. Initially it metabolizes in the liver with cytochrome P450 isoenzymes, followed by a glucuronidation reaction catalyzed by the UGT1A4 enzyme. Material and method. In order to minimize the side effects, new therapeutic approaches are sought to increase the success of the therapy. Conclusions. Biodegradable nano-tools that deliver anastrozole to the target site with an increase in its half-life to 144 hours are a promising method. A similar effect can be achieved by using a transdermal anastrozole administration system, which is a completely non-invasive method of treatment.

Can we prevent breast cancer?

After introducing reasons why prevention of breast cancer is needed, this proposal for preventing breast cancer with the drugs tamoxifen and gestodene is presented. Improvements in treatment of breast cancer by local surgery and adjuvant therapy can be expected to be modest at best. Screening may prevent some deaths, but is not cost effective, since the majority of cancer patients will still die. The hope of preventing breast cancer with a low fat diet is still unproven, and epidemiologic evidence so far suggests that long-term diets with 20% fat, probably taken during youth, are needed. Much more likely to be successful is formulating an oral contraceptive, and/or a post-menopausal estrogen supplement, with a steroid that prevents breast cancer. There is evidence that the new progestogen gestodene inhibits growth of breast neoplastic cells. It may work during the progression of neoplasm, displace estradiol from the cancer cell estrogen receptor, and cause breast cancer cells to secrete the negative growth modulator called TGF beta. The anti-estrogen *tamoxifen is another agent that may prove useful in preventing breast cancer. It is cytostatic for tumor cells, inhibits initiation and promotion of cancer growth, is an effective palliative treatment for existing cancer in post-menopausal women, and may even raise high-density lipoprotein cholesterol. More work needs to be done on tolerance of side effects, its biological effects on coagulation, lipid and bone metabolism, psychological and sexual consequences and its effect on cancer in pre-menopausal women. The ethics and feasibility of designing clinical trials of these drugs are discussed.