Chemotherapeutic Approaches for Targeting Cell Death Pathways

Abstract

Learning Objectives After completing this course, the reader will be able to: List the multiple cell death pathways that are activated in response to chemotherapeutic agents. Identify signaling molecules involved and morphological changes that occur in the different types of cell death pathways. Describe mechanisms targeted by novel chemotherapeutic agents. Access and take the CME test online and receive 1 AMA PRA category 1 credit at http://CME.TheOncologist.com For several decades, apoptosis has taken center stage as the principal mechanism of programmed cell death in mammalian tissues. It also has been increasingly noted that conventional chemotherapeutic agents not only elicit apoptosis but other forms of nonapoptotic death such as necrosis, autophagy, mitotic catastrophe, and senescence. This review presents background on the signaling pathways involved in the different cell death outcomes. A re‐examination of what we know about chemotherapy‐induced death is vitally important in light of new understanding of nonapoptotic cell death signaling pathways. If we can precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, perhaps we can succeed in more effective and less toxic chemotherapeutic regimens.

Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma

“…This synergic cytotoxicity might be due to apoptosis. 44 In the present in vivo study, the adequate dose of oxaliplatin and gemcitabine was determined by balancing the resulting cellular toxicity and safety profile. The oxaliplatin dose was similar to that used in the previous study.…”

Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death

“…Currently, the majority of clinical chemotherapeutic agents ultimately induce tumor cell apoptosis following treatment, however, noting the facts that many cancers have defective apoptosis machinery or aquire apoptosis resistance during therapy [36], or the finding, that apoptosis may be reversed in cancer cells [37], it is reasonable to consider whether activating alternative cell death pathways, such as necrosis, may be another effective strategy for cancer therapy [38]. Unlike apoptosis which is largely immune silent or immunosuppressive, therapy-induced necrotic cell death initiates an immune response to tumor cells [39].…”

Sporamin induces apoptosis and inhibits NF-κB activation in human pancreatic cancer cells

“…5,6 Chemotherapy-induced tumor cell apoptosis by regulation of signaling pathways has become the principle strategy in tumor chemotherapeutics. 7 However, most of the chemotherapeutics for PC have great aversive side effects, 2 so it is necessary for us to find a proper therapeutic strategy for PC patients. Sporamin, a Kunitz-type trypsin inhibitor (TI), is the major soluble storage protein in sweet potato tuberous roots, which can induce anti-tumor effects in several cancer cell lines, such as human leukemia HL60 cells, human tongue cancer Tca8113 cells, and human colorectal cancer HCT-8 cells.…”