Targeted Therapy News Articles
Aggarwal BB, Shishodia S
posted November 2006
While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways.
In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots) and dietary fiber.
For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2 and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food. (complete article in Biochem Pharmacol. 2006 May 14;71(10):1397-421)
The Chemistry Core Facility (CCF) is open and ready for business.
A program of the Center for Targeted Therapy located on the MD Anderson campus, the CCF assists MD Anderson investigators with the design, synthesis, development and manufacture of compounds of biological interest.
Under the direction of John McMurray, Ph.D., associate professor, Waldemar Priebe, Ph.D., professor, both in the Department of Experimental Therapeutics, and William Bornmann, Ph.D., professor in the Department of Experimental Diagnostic Imaging, the CCF will benefit investigators with NIH, ACS, other peer-reviewed grants, sponsored research contracts and institutionally-funded research projects (e.g., funded by the TRC).
The CCF is able to manufacture specific compounds for use in research at MD Anderson. For instance, if a small amount of a previously reported compound is needed for antitumor and biological testing, but is difficult to obtain from a pharmaceutical company, the compound can be legally synthesized by the chemists in the CCF and used for non-human applications. Examples of this type of service include the synthesis of SAHA, Gleevec and BMS-354825.
New compounds can also be designed and synthesized to order with desired chemical properties and biological activity against molecular targets. The CCF scientists can develop analogs to known classes of compoounds and modify existing drugs to enhance their therapeutic effects.
For more information regarding the Chemistry Core Facility and its services, please contact Dr. John McMurray at 713-795-3763 or via email at firstname.lastname@example.org.
April 14, 2006
Michael Rosenblum, Ph.D., professor of cancer medicine in the Department of Experimental Therapeutics, and collaborators here and around the world have developed two new potential anticancer agents: one to treat melanoma and certain aggressive types of breast tumors and another to inhibit blood vessel development in solid tumors and in breast and prostate cancer bone metastasis.
What’s especially newsworthy is that the design, construction and pre-clinical studies of the two fusion proteins (scFvMEL/TNF and VEGF121/rGel) were accomplished completely internally at MD Anderson Cancer Center. Dr. Rosenblum says, “Concept design through testing and on to the clinic, all within MD Anderson, is unique to cancer institutions. It gives us the capability to focus on agents that fill unmet medical needs, needs that might never be addressed otherwise.”
The fusion protein scFvMEL/TNF is an antibody that delivers tumor necrosis factor, a protein that promotes cell death for both melanoma and breast cancer cells that express the antigen gp240. By contrast, the fusion protein VEGF121/rGel not only inhibits breast cancer and prostate cancer metastasis, but also targets the developing blood vessels in all solid tumors. A Phase I trial for each agent is planned for June 2006, and will be chaired by Luis Camacho, M.D., and Razelle Kurzrock, M.D., respectively.
From the discovery in the laboratory through agent development and synthesis and finally through clinical testing, the collaborative processes and massed resources which will be concentrated in the Center for Targeted Therapy at the McCombs Institute will take years off the traditional way drugs have been developed and will help to move effective treatments into the clinic for cancer patients faster than ever before.
March 8, 2006
Curcumin, the pungent yellow spice found in both turmeric and curry powders, inhibited progression of the disease to the lungs of mice with breast cancer. The MD Anderson study, published in the October 15, 2005, issue of the journal Clinical Cancer Research, showed that the spice appears to shut down a protein active in the spread of breast cancer to the lung, a major target for metastasis.
In the August 15, 2005, issue of the journal Cancer, MD Anderson researchers reported that curcumin blocks a key biological pathway needed for development of melanoma and other cancers. They demonstrated that curcumin stops laboratory strains of melanoma from proliferating and forces the cancer cells to self-destruct. It does this by shutting down a powerful protein (NF-kB) that is known to promote an abnormal inflammatory response that leads to a variety of disorders, including arthritis and cancer. Also, dramatic results from MD Anderson laboratory studies led to two ongoing Phase I human clinical trials, testing the ability of curcumin powder to retard growth of pancreatic cancer and multiple myeloma. More about curcumin... [ext link object to Network article]
Crossing the Blood-Brain Barrier to Target Brain Tumors
February 6, 2006
Reported at American Association for Cancer research meeting - November, 2005
Waldemar Priebe, Ph.D., professor of medicinal chemistry, and colleagues Charles Conrad, M.D., associate professor of neuro-oncology, Timothy Madden, Pharm.D., associate professor of pharmacology, and Izabela Fokt, Ph.D., instructor of medicinal chemistry at MD Anderson, have designed, synthesized and evaluated the first agent capable of crossing the blood-brain barrier and targeting topoisomerase II, a protein associated with malignant gliomas, the most aggressive form of brain tumors. At the November 2005 meeting of the American Association for Cancer Research in Philadelphia, Priebe revealed that the drug, licensed by Reata Pharmaceuticals, is beginning Phase I clinical trials and plans to enroll up to 30 patients with advanced brain cancer. The agent also has promise for treating other cancers that tend to metastasize to the brain.