Abstract 2039: Potential therapeutic peptides for neuroblastoma.
Authors: Malkas Linda H. , Gu Long , Li Mingway , Smith Shanna , Lingeman Robert , Wuenschell Gerald , Zhang Lei , Hickey Robert 
Published: August 2014

Neuroblastoma (NB) is a form of cancer that starts in certain types of very primitive developing nerve cells found in an embryo or fetus. This type of cancer occurs in infants and young children. It is rarely found in children older than 10 years. NB is by far the most common cancer in infants (less than 1 year old). It accounts for about 7% of all cancers in children. There are approximately 650 new cases of NB each year in the United States. The types of treatment used may include surgery, chemotherapy, retinoid therapy, and radiation therapy. In many cases, especially when the cancer has spread too far to be completely removed by surgery, chemotherapy is the main treatment. Most children with NB will need to have chemotherapy. In most cases, treatment involves a combination of anticancer drugs. These therapies by-in-large always have significant side-effects. The goal of all therapies aimed at eradicating cancer, including NB, is to selectively destroy cancer cells while sparing normal tissue. Most chemotherapeutic or radiotherapeutic agents function by damaging DNA or interfering with DNA replication. Rapid advances in recent years have contributed significantly to identifying and understanding the roles of key proteins in DNA damage response pathways. (As a result, the nuclear protein PCNA has been shown to be a component of all DNA replication/repair processes in the human cell). Logically then, it is reasonable to assume that by altering the cellular response to DNA damage, perhaps through manipulating genes or proteins related to DNA repair, cell cycle checkpoint control, damage tolerance or apoptosis, the effectiveness of conventional cancer therapy can potentially be enhanced or used as novel targets for drug discovery. Of course, also selectively sensitizing cancer cells relative to normal tissues should improve the therapeutic ratio for anti-cancer treatment. Our laboratory's recent data indicate that the use of PCNA derived synthetic peptides promote NB cytotoxicity. The hypothesis driving our work is that specific peptides derived from the PCNA protein sequence (caPeptides) have the potential ability to block the binding of several cellular proteins that participate in DNA replication, repair, cell cycle control, transcription, and chromosomal recombination in cancer cells to full length PCNA. By disrupting the naturally occurring interaction between PCNA and the proteins that bind to, or interact, with PCNA, cellular functions that recruit PCNA would be disrupted in the NB cell. These peptides, either alone or in combination with other cancer therapy agents are potentially useful cancer chemotherapeutics or augmentors of the pharmacodynamic effect of specific anti-cancer chemotherapeutics.

Citation Format: Linda H. Malkas, Long Gu, Mingway Li, Shanna Smith, Robert Lingeman, Gerald Wuenschell, Lei Zhang, Robert Hickey. Potential therapeutic peptides for neuroblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2039. doi:10.1158/1538-7445.AM2013-2039