Introduction

Over the past several years, knowledge of molecular mechanisms regulating normal and aberrant cell growth leading to tumor formation has been enhanced. Although human cancers are biologically and pathologically quite distinct, it is surprising that perturbation of the p53 pathway occurs in most, if not all, types of human cancers, highlighting the central role of p53 in tumor development. p53 inactivation determines a condition of genetic instability, justifying the subsequent susceptibility to acquire mutations of different other genes. Alterations to p53 gene appear to have little or no prognostic value for patients treated by surgery alone, but are associated with worse survival for patients treated with chemotherapy. Studies have begun to identify markers predicting whether a tumor will respond to a particular chemotherapy. The ultimate goal is to prospectively identify patients who should receive chemotherapy and to tailor the treatment to the molecular profile of the tumor and the patient. Such an approach has the potential to dramatically improve response rates. The role of new biomarkers, such as p53, seems to be very promising in predicting prognosis and sensitivity to chemotherapy, thus representing the first step toward a better definition of therapeutic strategies according to the molecular characterization of individual patients. Treatments that depend on the p53 pathway require the scanning of the entire p53 gene and the identification of any type of mutation. Several diagnostic strategies have been developed to identify mutations in the p53 gene; among these, automated direct sequence analysis remains the most precise method for high-throughput screening of a wide range of mutations. The improvement of the emerging chip technology will represent the most advanced alternative. Novel strategies are emerging for the treatment of tumors that have p53 mutations. There are several approaches leading to the restoration of the normal p53 function: the most direct one involves gene therapy used to transfer the wild-type p53 gene to cancer cells that express mutant p53; other ambitious strategies aim to convert mutant p53 protein into its wild-type form by using small peptides, or by introducing drugs that disrupt the interaction between viral and cellular proteins and p53; and another angle of attack is provided by the stimulation of the host's immune response to mutant p53.

We report an overview of the p53 status in tumors, major methods for screening p53 mutations, and therapeutic approaches suggested for restoring p53 function.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment