Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy: Targeted Therapies to Reverse Resistance (Resistance to Targeted Anti-Cancer Therapeutics Book 1)

This volume gives the latest developments in on the mechanisms of cancer cell resistance to apoptotic stimuli, which eventually result in cancer progression and metastasis. One of the main challenges in cancer research is to develop new therapies to combat resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance to cytotoxic drug-induced apoptosis. These mechanisms should reveal gene products that directly regulate resistance in order to develop new drugs that target these resistance factors and such new drugs may either be selective or common to various cancers. If successful, new drugs may not be toxic and may be used effectively in combination with subtoxic conventional drugs to achieve synergy and to reverse tumor cell resistance. The research developments presented in this book can be translated to produce better clinical responses to resistant tumors. Patients with various cancers are treated with conventional chemotherapeutic drugs and the majority responds well to such therapies. However, there is a subset of patients who does not respond initially and another subset who no longer responds to further treatments. Clearly, in those two subsets of patients, the cancer cells exhibit mechanisms of resistance. One of the main challenges facing us to date is to develop new therapies to treat patients with the resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance. Such mechanisms have revealed gene products that directly regulate resistance and are targets for therapy. Of interest, several FDA-approved drugs were able to overcome drug resistance and have been successfully used clinically. They have been used as monotherapy or synergized with other therapies for the treatment of resistant tumors. This volume constitutes a total of twelve selective reviews by pioneer scientists in the field of cancer drug resistance. Specific mechanisms in drug resistance are reviewed and novel approaches are being proposed for therapeutic interventions. This volume is of general interest to scientists, clinicians, health care providers, and students. Front Matter....Pages i-xiii Multidrug Resistance in Cancer: A Tale of ABC Drug Transporters....Pages 1-34 Multidrug Resistance: A Role for Membrane Physics, pH and Drug Transporters....Pages 35-46 Mechanisms and Potential Therapies for Acquired Resistance to Inhibitors Targeting the Raf or MEK Kinases in Cancer....Pages 47-67 Mechanisms of Resistance to Targeted B-Raf Therapies....Pages 69-88 Role of β1 Integrins in the Complication and Drug Resistance Against Lung Cancer: Targeting β1 Integrins to Eradicate Lung Cancer....Pages 89-108 Aldo-Keto Reductases as New Therapeutic Targets for Colon Cancer Chemoresistance....Pages 109-133 Overcoming Drug Resistance Through Elevation of ROS in Cancer....Pages 135-149 Cancer Stem Cells in Resistance to Cytotoxic Drugs: Implications in Chemotherapy....Pages 151-161 Two Birds with a Stone: Molecular Cancer Therapy Targeting Signal Transduction and DNA Repair Pathways....Pages 163-186 Collateral Sensitivity in Drug-Resistant Tumor Cells....Pages 187-211 Human Cancer Resistance to Trail-Apoptotic Pathway-Targeted Therapies....Pages 213-243 The Dark Side of Apoptosis....Pages 245-258 Erratum to: Overcoming Drug Resistance Through Elevation of ROS in Cancer....Pages E1-E3 Back Matter....Pages 259-260