Chemotherapy resistance is an important problem often encountered during the course of breast cancer treatment. In order to design rational and efficacious therapies, the molecular mechanisms used by cells to develop resistance must be investigated. One mechanism employed by cancer cells is to alter cell signaling. This review examines the role of mitogen-activated protein kinases (MAPKs) and their endogenous negative regulators, mitogen-activated protein kinase phosphatases (MKPs), in chemotherapy resistance in breast cancer. MAPK signaling is activated in response to both growth factors and cellular stress. MKPs dephosphorylate MAPKs and are part of the dual-specificity family of phosphatases. MAPKs have been shown to be involved in resistance to tamoxifen, and MKPs have been linked to resistance to treatment with doxorubicin, mechlorethamine, paclitaxel, proteasome inhibitors, and oxidative-stress-induced cell death in breast cancer. The role of MKPs in tamoxifen resistance and the elucidation of the mechanisms involved with resistance to standard chemotherapy agents need to be investigated further. Growing evidence suggests that modulating MKP-1 activity could be a viable option to make breast cancer chemotherapy more effective.

Deregulation of cell signaling is a vital part of cancer development. The mitogen activated protein kinase (MAPK) family is involved in regulating both cell growth and cell death. This family of kinases is negatively regulated by mitogen activated protein kinase phosphatases (MKPs). MKPs are dual specificity phosphatases that target threonine and tyrosine residues that appear in a TXY motif. There are eleven members of the MKP family. Expression of MKPs has been shown to be altered in many different types of cancer. Most of what is known centers on MKP-1, MKP-2 and MKP-3. This review will focus on their role in cancer development and progression.

IMPORTANCE Targeted drug delivery (TDD) has potential for cost savings compared with conventional medical management (CMM). Despite positive clinical and economic evidence, TDD remains underused to treat cancer pain. OBJECTIVE To assess the cost of TDD and CMM in treating cancer-related pain. DESIGN, SETTING, AND PARTICIPANTS This retrospective economic evaluation using propensity score-matched analysis was conducted using MarketScan commercial claims data on beneficiaries receiving TDD and CMM or CMM only for cancer pain from January 1, 2009, to September 30, 2015. Participants were matched on age, sex, cancer type, comorbidity score, and pre-enrollment characteristics. Data analysis was performed from June 1 to September 30, 2017. MAIN OUTCOMES AND MEASURES Total 2-, 6-, and 12-month costs, number of health care encounters, length of hospital stay, additional components of cost, and health care utilization. RESULTS A total of 376 TDD and CMM patients (mean [SD] age, 51.88 [9.98] years; 216 [57.5%] female) and 4839 CMM only patients (mean [SD] age, 51.52 [11.16] years; 3005 [62.1%] female) were identified for study inclusion. After matching, 536 patients were included in the study: 268 patients in the TDD and CMM group and 268 in the CMM only group.

No abstract