The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Hormone receptor-positive breast cancer is usually subjected to hormone therapy, while triple-negative breast cancer is more formidable and poses a therapeutic challenge. Glucose transporters are potential targets for the development of anticancer drugs. In search of anticancer agents whose effect could be enhanced by a GLUT1 inhibitor WZB117, we found that MK-2206, a potent allosteric Akt inhibitor, when combined with WZB117, showed a synergistic effect on growth inhibition and apoptosis induction in breast cancer cells, including ER(+) MCF-7 cells and triple-negative MDA-MB-231 cells. The combination index values at 50% growth inhibition were 0.45 and 0.21, respectively. Mechanism studies revealed that MK-2206 and WZB117 exert a synergistic cytotoxic effect in both MCF-7 and MDA-MB-231 breast cancer cells by inhibiting Akt phosphorylation and inducing DNA damage. The combination may also compromise DNA damage repair and ultimately lead to apoptosis. Our findings suggest that the combination of Akt inhibitors and GLUT1 inhibitors could be a novel strategy to combat breast cancer.
Among women with metastatic breast cancer, use of an investigational oral form of paclitaxel yielded a higher overall response rate than the IV form, but administration was unique and time-consuming.Medscape Medical News
Publication date: Available online 12 December 2019Source: The LancetAuthor(s): Jack Cuzick, Ivana Sestak, John F Forbes, Mitch Dowsett, Simon Cawthorn, Robert E Mansel, Sibylle Loibl, Bernardo Bonanni, D Gareth Evans, Anthony Howell, IBIS-II investigatorsSummaryBackgroundTwo large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo...
ConclusionSingle isocenter technique was not feasible as the telecobalt unit did not have multileaf collimators and asymmetric jaws. With improved image based planning, a multi-isocentric technique was planned. By evaluating the dose distribution, beam modifications can be made and treatments can be given with acceptable toxicity.
Estrogen alone and estrogen/progestin have opposite effects on breast cancer risk; adding progestin may lead to a lifetime of increased risk.Medscape Medical News
Women who use certain types of hormones after menopause may still have an increased risk of developing breast cancer nearly two decades after they stop taking the pills
In postmenopausal women, breast cancer incidence down with estrogen alone, up with CEE + MPA
In conclusion, we identified and mechanically confirmed that AK4 is a novel therapeutic target of HER2-positive breast cancer. PMID: 31827645 [PubMed - in process]
More than 27,000 women in the US were given a hormone replacement therapy or a placebo - oestrogen-only HRT was found to reduce cancer risk by 23 per cent while combined HRT raised it.
Conclusions: The improved lesion segmentation method gives more precise lesion edge, which not only saves the time of automatic extraction of lesion region of interest without threshold setting for each case, but also prevents the segmentation error by manual and prejudice from different radiologists. The feature selection algorithm of multimodel-based recursive feature elimination has the ability to find robust and optimal features that distinguish the four molecular subtypes from image phenotypes. The gradient boosting decision tree classifier rather plays a main role in recognition than other models used in this paper. ...
A new tool could make it easier to predict whether early-stage triple-negative breast cancer will return following chemotherapy, according to results of a trial using a liquid biopsy to detect circulating tumor DNA.