Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases. (June 2018)

• Record Type: Journal Article
• Authors: Shah, Neal; Mohammad, Afroz S.; Saralkar, Pushkar; Sprowls, Samuel A.; Vickers, Schuyler D.; John, Devin; Tallman, Rachel M.; Lucke-Wold, Brandon P.; Jarrell, Katherine E.; Pinti, Mark; Nolan, Richard L.; Lockman, Paul R.
• Is Part Of: Pharmacological research. Volume 132(2018)
• Page Start: 47
• Page End: 68
• Publication Date: 2018-06
• Subjects: 5-Azacitidine (PubMED CID: 9444) -- 5-Fluorouracil (PubMED CID: 3385) -- Afatinib (PubMED CID: 10184653) -- Abemaciclib (PubMED CID: 46220502) -- Alisertib (PubMED CID: 24471867) -- Alpelisib (PubMED CID: 56649450) -- Anastrozole (PubMED CID: 2187) -- Apitolisib (PubMED CID: 25254071) -- Bleomycin (PubMED CID: 5360373) -- Brilanestrant (PubMED CID: 56941241) -- Buparlisib (PubMED CID: 16654980) -- Cabozantinib (PubMED CID: 25102847) -- Capecitabine (PubMED CID: 60953) -- Carmustine (PubMED CID: 2578) -- Cisplatin (PubMED CID: 84691) -- Cyclophosphamide (PubMED CID: 2907) -- Cytarabine (PubMED CID: 6253) -- Dactolisib (PubMED CID: 11977753) -- Daunorubicin (PubMED CID: 30323) -- Docetaxel (PubMED CID: 148124) -- Doxorubicin (PubMED CID: 31703) -- Elacestrant (PubMED CID: 23462301) -- Entinostat (PubMED CID: 4261) -- Eribulin (PubMED CID: 17755248) -- Estradiol (PubMED CID: 5757) -- Etirinotecan pegol (PubMED CID: 71300725) -- Etoposide (PubMED CID: 36462) -- Everolimus (PubMED CID: 18477728) -- Exemestane (PubMED CID: 60198) -- Fulvestrant (PubMED CID: 104741) -- Gemcitabine (PubMED CID: 60750) -- Goserelin (PubMED CID: 5311128) -- Ifosfamide (PubMED CID: 3690) -- Iniparib (PubMED CID: 9796068) -- Irinotecan (PubMED CID: 60838) -- Lapatinib (PubMED CID: 208908) -- Lenvatinib (PubMED CID: 9823820) -- Letrozole (PubMED CID: 3902) -- Leuprorelin (PubMED CID: 657181) -- Lomustine (PubMED CID: 3950) -- Methotrexate (PubMED CID: 126941) -- Mitoxantrone (PubMED CID: 4212) -- Neratinib (PubMED CID: 9915743) -- Olaparib (PubMED CID: 23725625) -- Palbociclib (PubMED CID: 122706004) -- Paclitaxel (PubMED CID: 36314) -- Pictilisib (PubMED CID: 17755052) -- Pilaralisib (PubMED CID: 56599306) -- Ribociclib (PubMED CID: 44631912) -- Rucaparib (PubMED CID: 9931954) -- Sonidegib (PubMED CID: 24775005) -- Sunitinib (PubMED CID: 5329102) -- Tamoxifen (PubMED CID: 2733526) -- Taselisib (PubMED CID: 51001932) -- Temozolomide (PubMED CID: 5394) -- Teniposide (PubMED CID: 452548) -- Topotecan (PubMED CID: 60700) -- Tucatinib (PubMED CID: 51039094) -- Veliparib (PubMED CID: 11960529) -- Vincristine (PubMED CID: 5978) -- Vinorelbine (PubMED CID: 5311497) -- Voxtalisib (PubMED CID: 49867926) -- Z-Endoxifen (PubMED CID: 10090750); ABC accelerated blood clearance -- BBB blood-brain barrier -- BCBM breast cancer brain metastases -- BTB blood-tumor barrier -- CNS central nervous system -- CDK cyclin-dependent kinase -- EPR enhanced permeation and retention -- ER estrogen receptor -- HDAC histone deacetylase -- HER2 human epidermal growth factor receptor 2 -- HR Hormone receptor -- MBCB metastatic breast cancer of the brain -- mTOR mammalian target of rapamycin -- OS overall survival -- P-gp permeability glycoprotein -- PARP poly-ADP ribose polymerase -- PEG polyethylene glycol -- PFS progression-free survival -- PI3K phosphatidylinositide 3-kinase -- PEG polyethylene glycol -- PR progesterone receptor -- SRS stereotactic radiosurgery -- T-DM1 trastuzumab emtansine -- TNBC triple negative breast cancer -- VEGF vascular endothelial growth factor -- WBRT whole-brain radiation therapy; Breast cancer brain metastases -- Novel chemotherapy -- Nanoparticles -- Liposomes -- Pegylation -- Clinical trials; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2018.03.021
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms. We provide a historical overview of BCBM chemotherapy, review the mechanisms of new agents such as poly-ADP ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, phosphatidyl inositol 3-kinaseinhibitors, estrogen pathway antagonists for hormone-receptor positive BCBM; tyrosine kinase inhibitors, antibodies, and conjugates for HER2 + BCBM; repurposed cytotoxic chemotherapy for triple negative BCBM; and the utilization of these new agents and formulations in ongoing clinical trials. The mechanisms of novel dosage formulations such as nanoparticles, liposomes, pegylation, the concepts of enhanced permeation and retention, and drugs utilizing these concepts involved in clinical trials are also discussed. These new treatments provide a promising outlook in the treatment of BCBM.