Cisplatin anti-cancer drug binds pervasively to RNA....

In continuation of my update on Cisplatin.....

An anti-cancer drug used extensively in chemotherapy binds pervasively to RNA -- up to 20-fold more than it does to DNA, a surprise finding that suggests new targeting approaches might be useful, according to University of Oregon researchers, lead by Victoria J. DeRose

Ref : http://uonews.uoregon.edu/archive/news-release/2011/11/cancer-drug-cisplatin-found-bind-glue-cellular-rna

Gemcitabine and cisplatin a promising combination for endometrial cancer...

In continuation of my update on cis-platin and its importance, I find this  info interesting to share with...

Gemcitabine (see structure) and cisplatin in combination have been investigated extensively in other disease sites, and synergism of the two agents has been confirmed in cell lines of human endometrial, ovarian, colon, lung and squamous cell head and neck carcinoma

Now researchers from The University of Texas M. D. Anderson Cancer Center , lead by Dr.Jubilee Brown, report from a small study of women with advanced or recurrent endometrial cancer, that gemcitabine and cisplatin, when used in combination, produced a response rate in fifty percent of patients.

The Phase II study of 20 patients found that the combination of gemcitabine and cisplatin, two drugs currently used to treat other types of cancer, limited the disease's progression, increasing progression-free survival while maintaining tolerable toxicity levels. It is believed that when administered together, gemcitabine helps overcome cell resistance to cisplatin, throwing tumor cells a potent one-two punch.


Findings demonstrated a 50 percent overall response rate, or improvement in disease. Additionally, the clinical benefit of the two-drug combination was 80 percent, as 16 of the 20 women experienced either an improvement or stabilization of disease. All side effects resulting from the therapy were manageable. Lead researcher, Dr. Brown concluded  that results from the study warrant investigation of the chemotherapy combination in a larger, definitive trial at multiple institutions.....

Ref :  Dr. Jubilee Brown, http://www.mdanderson.org/

Triapine with cisplatin a new standard of care for cervical cancer?

In continuation of my update on cancer drug development,   I found this  info interesting to share with. Researchers  lead by Dr. Charles Kunos at the Ireland Cancer Center of University Hospitals (UH)  have found that,  Triapine, (3-aminopyridine-2-carbox -aldehyde   thiosemicarbazone, see structure), which suppresses tumor growth shows a great deal of promise for cervical cancer patients who are at high risk for relapse and cancer-related death. 

The phase I study found that the chemotherapy medicine  Triapine, was well tolerated in combination with standard-of-care cisplatin chemotherapy and radiation treatment in women with cervical cancer. This regimen provided both significant reduction in cancer disease and cancer control.

In the study   (ten-patient study) patients,  were treated three times weekly with Triapine (a potent Ribonucleotide Reductase Inhibitor) in combination with weekly cisplatin treatment and daily pelvic radiation therapy over five weeks.  The researchers claims that  "a 100% complete response rate was observed and no disease progression was documented through 18 months of median follow-up."A phase two follow-up study is ongoing at the Ireland Cancer Center. UH Case Medical Center  Hope this new found combintaton will be  a promising new treatment to help women fight this aggressive disease in the days to come...

Ref : http://clincancerres.aacrjournals.org/content/16/4/1298.abstract?sid=f3df7c2d-9e46-4baf-b47b-83d310b87641

Mitaplatin as a better anticancer agent.......

In continuation of my update on Platinum compounds as anticancer drugs, I find  this one more interesting info to share with. MIT chemists have developed a new platinum compound that is as powerful as the commonly used anticancer drug cisplatin but better able to destroy tumor cells.

As per the claim by the researchers, glycolytic metabolism of most solid tumors, known as the Warburg effect, is associated with resistance to apoptosis that enables cancer cells to survive. Dichloroacetate (DCA) is an anticancer agent that can reverse the Warburg effect by inhibiting a key enzyme in cancer cells, pyruvate dehydrogenase kinase (PDK), that is required for the process. DCA is currently not approved for cancer treatment in the USA. With this idea behind researchers have prepared the new compound by combining dichloroacetate, DCA and cisplatin. Mitaplatin, thus obtained has two DCA units which are appended to the axial positions of a six-coordinate Pt (IV) center.

As per the claim by the authors, the negative intracellular redox potential reduces the platinum to release cisplatin, a Pt (II) compound, and two equivalents of DCA. By a unique mechanism, mitaplatin thereby attacks both nuclear DNA with cisplatin and mitochondria with DCA selectively in cancer cells. The cytotoxicity of mitaplatin in a variety of cancer cell lines equals or exceeds that of all known Pt (IV) compounds and is comparable to that of cisplatin.

Mitaplatin alters the mitochondrial membrane potential gradient of cancer cells, promoting apoptosis by releasing cytochrome c and translocating apoptosis inducing factor from mitochondria to the nucleus. Cisplatin formed upon cellular reduction of mitaplatin enters the nucleus and targets DNA to form 1,2-intrastrand d(GpG) cross-links characteristic of its own potency as an anticancer drug. These properties of mitaplatin are manifest in its ability to selectively kill cancer cells cocultured with normal fibroblasts and to partially overcome cisplatin resistance. Further studies like mice transplanted with human tissues are to be substantiated, in my opinion its a good achievement...

Ref : http://www.pnas.org/content/early/2009/12/09/0912276106.abstract?related-urls=yes&legid=pnas;0912276106v1

Oncolytics Biotech's REOLYSIN combined with paclitaxel and carboplatin well tolerated for advanced cancers

In continuation of my follow up on cisplatin derivatives, I find this article interesting to share with.....

Oncolytics Biotech's REOLYSIN combined with paclitaxel and carboplatin well tolerated for advanced cancers

Picoplatin a better drug than oxaliplatin for colorectal cancer !

In one of my earlier blog, I did mention about the Cisplatin (Cisplatin doubles lung cancer survival time in mice !).

About Cis-platin & other drivatives:

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum(II) is a platinum-based chemotherapy drug used to treat various types of cancers, (sarcomas, some carcinomas (small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors. It was the first member of a class of anti-cancer drugs which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA which ultimately triggers apoptosis (programmed cell death).

Now its the turn of Picoplatin [see structure , Amminedichloro(2-methylpyridine)platinium)], Poniard Pharmaceuticals, Inc. has come up with some interesting results from its Phase 2 trial of picoplatin in patients with metastatic colorectal cancer (CRC). Picoplatin, given once every four weeks in combination with 5-fluorouracil and leucovorin in the FOLPI regimen, has comparable efficacy to oxaliplatin, given in combination with 5-fluorouracil and leucovorin in the modified FOLFOX-6 regimen, as a first-line therapy for CRC, as assessed by one-year survival rate, progression-free survival (PFS) and disease control. The company claims that, (from the updated proof-of-concept Phase 2 safety and efficacy results) picoplatin could be superior to oxaliplatin as a neuropathy-sparing alternative when used in combination as a first-line treatment for metastatic colorectal cancer.

Source : http://investor.poniard.com/ReleaseDetail.cfm?ReleaseID=424813.