Cancer therapy cisplatin

Berners-Price, S. J. Appleton, T. G. The Chemistry of Cisplatin in Aqueous Solution In Platinum-Based Drugs in Cancer Therapy. Kelland, L. R. Farrell, N., Eds. Humana Press Totowa, NJ, 2000. 

Cis-DiCHLORODiAMMiNEPLATiNUM (II) (cisplatin, CDDP) has been widely used for clinical cancer therapy in spite of its severe renal toxicity [1] and low water-solubility. 

The earliest combination chemotherapy and radiation trials in nonsmall-cell lung cancer included cisplatin and 5-fluorouracil and concurrent radiation therapy and found survival results comparable to those for sequential chemotherapy and radiation or to daily cisplatin and radiation therapy without surgery (119,121). Phase II studies of stage Ilia and Illb nonsmall-cell lung cancer patients treated with the combination of cisplatin with etoposide and 5 -fluorouracil and either single daily radiation fractionation or twice daily radiation fractionation prior to surgery produced similar clinical results (119,121). Complete surgical resection was accomplished in 70% of the patients, the median survival was 22 mo and the 2-yr survival rate was 45%. 

Brabec V. Chemistry and structural biology of 1,2-interstrand adducts of cisplatin. In (Kelland LR, Farrell N, eds) Platinum-Based Drugs in Cancer Therapy 2000 Humana Press Inc. Totowa, NJ pp. 37-61. 

The same multigenic approach can apply to cancer pharmacogenomic research, which may be especially relevant to cancer therapies that do not have an obvious candidate polymorphism in metabolism genes and do not have a major protein target, such as cisplatin-based chemotherapy and radiation therapy as well as combinatorial therapy with multiple agents. We will use cisplatin-based chemotherapy as a prototype to illustrate the application of using a pathway-based approach in pharmacogenomic studies. 

Finally, replication-competent viral vector systems have been combined with standard cancer therapy in animal models, resulting in synergistic effects. This has, for example, been shown for ONYX-015 plus cisplatin or ionizing radiation [108,112] and for an AdElB 55k-deleted virus expressing HSV-tk (plus ganciclovir) in combination with the topoisomerase inhibitor topotecan [114]. 

Niederle N, Schutte J, Schmidt CG (1986) Crossover comparison of the antiemetic efficacy of nabilone and alizapride in patients with nonseminomatous testicular cancer receiving cisplatin therapy. Klin Wochenschr 64 362-365... 

Metal-based drugs have probably had most impact in the area of cancer therapy, with cisplatin still used to treat approximately 70% of all cancer patients. Cisplatin is particularly useful for treatment of testicular, ovarian, oropharyngeal, bronchogenic, cervical, and bladder carcinomas, lymphoma, osteosarcoma, melanoma, and neuroblastoma. Metallocene-type compounds were the first organometallic compounds to be evaluated in cancer therapy, and until recently, Ti(77 -C5H5)2Cl2 was undergoing clinical trials (see above). Despite this setback to the field,... 

Use of dendrimers such as PAMAM, PPI and poly(ether hydro q lamine) (PEHAM) in drug deliveiy is mostly focused on cancer treatment. Dendrimers encapsulate anticancer drugs such as cisplatin and doxorubicin and agents for boron neutron capture therapy and photodynamic therapy. Cisplatin encapsulated dendrimers are reported to increase the bioavailability and selectivity of the drug on a solid tumor model which was provided by injection of B16F10 cells to C57 mice. ... 

Nevertheless, in some particular situations, CO can be considered a good choice for cancer treatment. Most of the data about CO s modulation of cell death indicate strong antiapoptotic properties, which is not compatible with chemotherapy strategies aiming the elimination of cancer cells. Thus, CORM-3 was used as an adjuvant in cancer therapy for limiting the antineoplastic agent cisplatin-induced nephrotoxicity [109], and CORM-2 was used for limiting doxorubicin-induced cardiotoxicity [79]. 

The compound on the right, cisplatin, is used in cancer therapy. Both compounds have a square-planar geometiy. Which compound has a nonzero dipole moment ... 

The chemotherapeutic cisplatin, cw-diamminedichloridoplatinum ii (CDDP), is widely used for the treatment of many malignancies, including testicular, ovarian, bladder, cervical, head and neck, and small cell and non-small cell limg cancers (1). There is a large amount of literature on the mechanisms of cisplatin-induced cell death, but its mode of action still remains unclear. Cisplatin may initiate the programmed cell death (apoptosis) via its binding to DNA, which may activate p5 3-dependent apoptotic pathways. Cisplatin, however, can also kill cancer cells with mutated p53 (2-4). Cisplatin may kill cells via multiple modes like apoptosis, necrosis, and perturbation of calciiun homeostasis (3-6). Understanding the mechanisms of cisplatin resistance and toxicity is an area of active research in cancer therapy. 

Liao Longyan, Liu Jenny, Dreaden C. Eiik, et al. A convergent synthetic platform for singlenanoparticle combination cancer therapy Ratiometric loading and controlled release of cisplatin, doxorubicin, and camptothecin. J. Am. Chem. Soc. 136 no. 16 (2014) 5896-5899. 

Dhar S, Kohshetti N, Lippard S J, Far OC. Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci 2011 108(5) 1850-5. 

---