ChemInform Abstract: Kinesin Spindle Protein (KSP) Inhibitors in Combination with Chemotherapeutic Agents for Cancer Therapy

Кidney injury is a frequent and significant complication of cancer and cancer therapy. The kidneys are susceptible to injury from malignant infiltration, damage by metabolites of malignant cells, glomerular injury, nephrotoxic drugs including chemotherapeutic agents. Also bone marrow transplantation complications, infections with immune suppression (including septicemia), tumor lysis syndrome should be taken into account. Chemotherapeutic agents are a common cause of acute kidney injury but can potentially lead to chronic kidney disease development in cancer patients. This article summarizes risk factors of acute kidney injury in cancer patients. Risk factors are divided into two groups. The systemic are decrease of total circulating blood volume, infiltration of kidney tissue by tumor cells, dysproteinemia, electrolyte disturbances. The local (renal) risk factors are microcirculation disturbances, drugs biotransformation with formation of reactive oxygen intermediates, high concentration of nephrotoxic agents in proximal tubules and its sensitivity to ischemia. Drug-related risk factors include: drugs combination with cytotoxic effect high doses long term use necessity, direct cytotoxic effect of not only chemotherapeutic agents but also its metabolites, mean solubility forming intratubular precipitates. Early diagnosis, timely prevention and treatment of these complications provide significantly improve nononcologic results of treatment.

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Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

Current Medicinal Chemistry ◽

10.2174/0929867325666180719145819 ◽

2020 ◽

Vol 27 (13) ◽

pp. 2118-2132 ◽

Cited By ~ 5

Author(s):

Aysegul Hanikoglu ◽

Hakan Ozben ◽

Ferhat Hanikoglu ◽

Tomris Ozben

Keyword(s):

Oxidative Stress ◽

Drug Resistance ◽

Side Effects ◽

Cancer Therapy ◽

Tumor Cells ◽

Anticancer Drugs ◽

Chemotherapeutic Agents ◽

Oxidation Reactions ◽

Hybrid Compounds ◽

Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

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Limitations in the Design of Chimeric Antigen Receptors for Cancer Therapy

Cells ◽

10.3390/cells8050472 ◽

2019 ◽

Vol 8 (5) ◽

pp. 472 ◽

Cited By ~ 30

Author(s):

Stefan Stoiber ◽

Bruno L. Cadilha ◽

Mohamed-Reda Benmebarek ◽

Stefanie Lesch ◽

Stefan Endres ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cancer Therapy ◽

Rational Design ◽

Chemotherapeutic Agents ◽

Therapeutic Modality ◽

T Cell Therapy ◽

Car T Cells ◽

Car T Cell ◽

Car T

Cancer therapy has entered a new era, transitioning from unspecific chemotherapeutic agents to increasingly specific immune-based therapeutic strategies. Among these, chimeric antigen receptor (CAR) T cells have shown unparalleled therapeutic potential in treating refractory hematological malignancies. In contrast, solid tumors pose a much greater challenge to CAR T cell therapy, which has yet to be overcome. As this novel therapeutic modality matures, increasing effort is being invested to determine the optimal structure and properties of CARs to facilitate the transition from empirical testing to the rational design of CAR T cells. In this review, we highlight how individual CAR domains contribute to the success and failure of this promising treatment modality and provide an insight into the most notable advances in the field of CAR T cell engineering.

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Kinesin Spindle Protein (KSP) Inhibitors. Part 2. The Design, Synthesis, and Characterization of 2,4-Diaryl-2,5-dihydropyrrole Inhibitors of the Mitotic Kinesin KSP.

ChemInform ◽

10.1002/chin.200628111 ◽

2006 ◽

Vol 37 (28) ◽

Author(s):

Mark E. Fraley ◽

et al. et al.

Keyword(s):

Synthesis And Characterization ◽

Design Synthesis ◽

Kinesin Spindle Protein ◽

Ksp Inhibitors

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De novo design, synthesis and biological evaluation of 1,4-dihydroquinolin-4-ones and 1,2,3,4-tetrahydroquinazolin-4-ones as potent kinesin spindle protein (KSP) inhibitors

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2011.07.029 ◽

2011 ◽

Vol 19 (18) ◽

pp. 5612-5627 ◽

Cited By ~ 17

Author(s):

Cheng Jiang ◽

Lei Yang ◽

Wu-Tong Wu ◽

Qing-Long Guo ◽

Qi-Dong You

Keyword(s):

De Novo ◽

De Novo Design ◽

Biological Evaluation ◽

Design Synthesis ◽

Kinesin Spindle Protein ◽

Ksp Inhibitors ◽

Synthesis And Biological Evaluation

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Cannabinoids and cancer: potential for colorectal cancer therapy

Biochemical Society Transactions ◽

10.1042/bst0330712 ◽

2005 ◽

Vol 33 (4) ◽

pp. 712-714 ◽

Cited By ~ 19

Author(s):

H.A. Patsos ◽

D.J. Hicks ◽

A. Greenhough ◽

A.C. Williams ◽

C. Paraskeva

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Therapy ◽

Surgical Techniques ◽

Chemotherapeutic Agents ◽

Signalling Pathways ◽

The World ◽

Endogenous Cannabinoids ◽

Tumour Cell Growth ◽

Stimulation Of

Despite extensive research into the biology of CRC (colorectal cancer), and recent advances in surgical techniques and chemotherapy, CRC continues to be a major cause of death throughout the world. Therefore it is important to develop novel chemopreventive/chemotherapeutic agents for CRC. Cannabinoids are a class of compounds that are currently used in the treatment of chemotherapy-induced nausea and vomiting, and in the stimulation of appetite. However, there is accumulating evidence that they could also be useful for the inhibition of tumour cell growth by modulating key survival signalling pathways. The chemotherapeutic potential for plant-derived and endogenous cannabinoids in CRC therapy is reviewed.

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