Poly-ADP ribose polymerase (PARP) proteins are critical mediators of DNA repair. Many traditional anti-cancer chemotherapy agents overwhelm a cell’s ability to repair DNA damage in order to kill proliferating malignant cells. Recent evidence suggests that cancers within and across tissue types have specific defects in DNA repair pathways, and that these defects may predispose for sensitivity and resistance to various classes of cytotoxic agents. Breast, ovarian and other cancers develop in the setting of inherited DNA repair deficiency, and these cancers may be more sensitive to cytotoxic agents that induce DNA strand breaks, as well as to inhibitors of PARP activity. A series of recent clinical trials has tested whether PARP inhibitors can achieve synthetic lethality in hereditary DNA repair-deficient tumors. At the current time, mutation of BRCA serves as a potential, but not comprehensive, biomarker to predict response to PARP inhibitor therapy. Mechanisms of resistance to PARP inhibitors are only recently being uncovered. Future studies seek to identify sporadic cancers that harbor genomic instability rendering susceptibility to PARP inhibitors that compound lethal DNA damage.

This book serves as a practical guide for the use of stereotactic body radiation therapy in clinics. On the basis of more than 10 years of clinical experience with lung cancer, liver cancer and other cancers, a remarkable volume of knowledge has been accumulated. At the same time, great progress in techniques has been achieved. Various new fixing apparatuses, new respiratory regulation techniques, new dose fractionation schedules and new image-guided radiation therapy machines have been developed. This book reviews the history of those developments and reports on various types of toxicities. Review of recent clinical studies is also included. The authors were key members of the JCOG 0403 clinical trials on stereotactic body radiation therapy (SBRT) for both inoperable and operableT1N0M0 primary lung cancer. Readers will learn of the superior outcomes obtained with SBRT for lung cancer and other cancers in terms of local control and toxicities. With its practical focus, this book will benefit radiation oncologists, medical physicists, medical dosimetrists, radiation therapists and senior nurses as well as medical oncologists and surgical oncologists who are interested in radiotherapy.

This book presents the first comprehensive exploration of the dynamic potential of microtubules anti-cancer targets. Written by leading anti-cancer researchers, this groundbreaking volume collects the most current microtubule research available and investigates the potential of microtubules in cancer therapy.

The treatment of prostate cancer continues to be problematic owing to serious side-effects, including erectile dysfunction and urinary incontinence. Robotic radiosurgery offers a novel, rapid, non-invasive outpatient treatment option that combines robotics, advanced image-guided spatial positioning, and motion detection with submillimeter precision. This book examines all aspects of the treatment of prostate cancer with robotic radiosurgery. It explains how image-guided robotic radiosurgery overcomes the problem of patient motion during radiation therapy by continuously identifying the precise location of the prostate tumor throughout the course of treatment. Hypofractionated radiation delivery by means of robotic radiosurgery systems is also discussed in detail. The book closes by examining other emerging genitourinary applications of robotic radiosurgery. All of the authors are experts in their field who present a persuasive case for this fascinating technique.

The development, clinical translation and recent efficacy of novel gene therapies targeting refractory malignancies has led to research that extends this technology to a variety of infectious and rheumatological diseases. Unlike conventional drugs or antibodies, T cells have the potential to target and exert effector function in response to disease in a dynamic manner, acting as a “living drug”. The most efficacious form of gene-modified T cells to date is the chimeric antigen receptor (CAR)-modified T cell, which redirects the specificity of T cells to an antigen expressed by tumor cells. Clinical experience with autologous CAR-T cells, primarily in hematologic malignancies, has underscored the feasibility and safety of the approach, while also demonstrating dramatic and sustained antitumor effects through mechanisms orthogonal to those of traditional anticancer therapies. However, several challenging obstacles must be surmounted in order to improve the broader efficacy of this approach.