PARP Inhibition in Triple Negative Breast Cancer

Patients with triple negative breast cancer have inherent defects in several DNA repair pathways. These cancer cells therefore become increasing dependent on another DNA damage repair pathway called base excision repair (BER) pathway, for survival. It so happens that PARP 1(PolyAdenosine diphosphate Ribose Polymerase) is an important enzyme regulating the BER pathway.  By inhibiting PARP1, the BER pathway is inhibited leading to extreme levels of DNA damage and eventual death of cancer cells.

In an article published in the Jan 20,2011 issue of the NEJM, the addition of a PARP inhibitor Iniparib to a combination of Carboplatin and Gemzar in patients with metastatic triple negative breast cancer, resulted in superior Response Rates, median Progression Free Survival and Overall Survival. This difficult -to -treat subtype of breast cancer may soon become extinct.

Improving Survival in Metastatic Pancreatic Cancer

A combination of Oxaliplatin, Irinotecan, Fluorouracil and Leucovorin (FOLFIRINOX) chemotherapy given to individuals with metastatic pancreatic cancer resulted in superior Response Rates, Progression Free Survival and Overall Survival compared to single agent Gemcitabine. For the first time, we now have a regimen that has demonstrated survival benefit for this hard-to-treat cancer.

This data was presented at the 2010 ASCO meeting

GVAX – Vaccine for Pancreatic Cancer

GVAX is a therapeutic cancer vaccine, developed to induce antitumor immunity. Traditional vaccination against specific bacterial and viral infections involves the injection of the specific weakened bacteria/virus or a structural component of the bacteria or virus. The body then mounts an immune response and is ready to respond to an infection associated with that specific bacteria or virus.

Based on the same principle GVAX, a cancer vaccine, comprises of patient derived tumor cells, that are irradiated to prevent it from dividing and is then genetically modified to secrete GM-CSF (Granulocyte Macrophage Colony Stimulating Factor). GM-CSF is important for the growth and activation of dendritic cells also known as Antigen Presenting Cells. This vaccine when injected activates the dendritic cells, which in turn stimulates the patients immune system to attack the vaccine tumor cells, which are in fact similar to the patients original tumor cells. This vaccine therefore theoretically boosts the body’s immune system to fight the patients tumor, without causing collateral damage.

The FDA granted Orphan Drug Status for GVAX vaccine to treat pancreatic cancer. An orphan drug is an agent developed to treat a rare medical disorder affecting fewer than 200,000 people in the United States.

GVAX vaccine is being studied in other types of cancer as well. It should however be noted that vaccines by themselves may be of benefit only for patients with low volume disease with adequately functioning immune system.