Belinostat

Belinostat (PXD101) is a novel HDAC inhibitor in late-stage clinical development with close to 1050 patients treated (March 2012). Belinostat is well tolerated which allows combination with traditional chemotherapy without causing further bone marrow toxicity. Pre-clinical experiments demonstrated belinostat to be effective against multiple cancers by inhibiting cell proliferation and inducing programed cell death (apoptosis), in tumor cells. This implies that belinostat prevents the cancer from growing and that the tumor cells are forced to self-destruct. Belinostat has been tested in a number of Phase I/II clinical trials in hematological cancers and solid tumors.

Data from these trials have provided proof of the anti-tumor effect of belinostat as monotherapy in peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), liver cancer, and thymoma. Additionally, it has been demonstrated that belinostat has beneficial effects in combination with other anti-cancer drugs for the treatment of multiple types of cancer including ovarian cancer, cancer of unknown primary (CUP), multiple myeloma, acute myeloid leukemia, and bladder cancer.

Drug resistance - a manifest problem

Drug resistance is the major obstacle in cancer treatment, and modern effective cancer therapy attempts to fight resistance by administering combinations of drugs that target cancer in different ways. However, the resistance problem is far from solved, and it is therefore important to find new cancer drugs that hit new targets. Cancer drugs can be divided into two groups identified by the specificity of their interaction with targets on the outside or within cancer cells. Some drugs interact with a single target, e.g. the herceptin interaction with the Her2 neu receptor, whereas other drugs are multi-targeted, e.g. drugs such as sorafenib, sunitinib, and belinostat. Hence their use is not limited to one single target.

From cancer models it is possible to find strong indications on how to optimize the use of such multi-targeted drugs. A limitation of many anti-cancer drugs is tolerability. Belinostat has low toxicity in patients and from markers it is indicated that the drug hits its biological target in cancer patients. As belinostat has limited toxicity in patients, the drug can be investigated in high doses as monotherapy as well as in almost all successful drug combinations. In tumor models studied at Topotarget, belinostat is active in cancer cells with resistance to existing therapies and belinostat adds substantial treatment improvement to several important drug combinations.

To access Topotarget belinostat trials click here

To access NCI- and Investigator Sponsored Trials (IST) click here