Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases

Neal Shah, Afroz S. Mohammad, Pushkar Saralkar, Samuel A. Sprowls, Schuyler D. Vickers, Devin John, Rachel M. Tallman, Brandon P. Lucke-Wold, Katherine E. Jarrell, Mark Pinti, Richard L. Nolan, Paul R. Lockman

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)47-68
Number of pages22
JournalPharmacological Research
Volume132
DOIs
StatePublished - Jun 2018

Bibliographical note

Funding Information:
This research was supported by a grant from the National Cancer Institute ( R01CA166067-01A1 ). Additional support for this research was provided through the National Institute of General Medical Sciences of the National Institutes of Health ( U54GM104942 , P30 GM103488 ), and the American Foundation for Pharmaceutical Education .

Keywords

  • Breast cancer brain metastases
  • Clinical trials
  • Liposomes
  • Nanoparticles
  • Novel chemotherapy
  • Pegylation

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