Shannon Puhalla, MD | Authors

Management of Breast Cancer Brain Metastases Is Moving Forward, but New Options Are Still Needed

July 15, 2014

Prevention of CNS seeding early in the metastatic disease course using drugs with both intra- and extracranial activity will be crucial to improving outcomes in patients with breast cancer brain metastases.

Triple-Negative Breast Cancer: Not Entirely Negative

September 15, 2013

Triple-negative breast cancer (TNBC) remains a very challenging entity today, but with the identification of new targets and further optimization of therapy, the landscape for TNBC may not look so negative. In the future, “TNBC” may be considered an antiquated misnomer, as we will have identified various breast cancer subgroups based on what they “are” rather than what they “are not.”

PARP Inhibitors in Breast Cancer: BRCA and Beyond

October 15, 2011

The aim of this article is to review the preclinical data and rationale for PARP inhibitor use in the aforementioned settings, as well as the current status of the clinical development of these agents in the treatment of breast cancer, along with future directions for research in this field.

PARP Inhibitors: What We Know and What We Have Yet to Know

January 16, 2010

Pharmacologic strategies targeting the DNA of tumor cells have been in use for much of the past century for many different cancer types. Radiation has also been a long-employed strategy to cause DNA damage and subsequent tumor cell death. However, the class of agents designed to inhibit the enzyme poly-(ADP-ribose) polymerase (PARP) have taken this a step further-these agents do not damage DNA themselves, but rather, inhibit the repair of DNA via inhibition of the base excision single-strand repair pathway. PARP inhibitors have been shown preclinically and clinically to enhance the affects of chemotherapies known to damage DNA or interefere with DNA replication. However, the most exciting use of PARP inhibitors may be in exploiting the concept of synthetic lethality. In this setting, the concept is based on two factors: (1) BRCA1/2-positive malignancies cannot use one of the major pathways to repair double-strand DNA breaks (ie, homologous recombination), and (2) making the base excision repair pathway nonfunctional via inhibition of PARP leads to tumor cell death, as unrepaired single-strand breaks are converted into double-strand breaks.

Bevacizumab in Breast Cancer: The Best Is Yet to Come?

April 09, 2009

Based on preclinical data, antiangiogeneic therapy for cancer is both logical and rational. Tumors secrete proangiogenic factors, and the design of agents that target these factors has great potential to add to and in some cases replace cytotoxic chemotherapy.