Mocetinostat is an investigational drug currently being studied for its potential role in cancer therapy. It has not yet been approved by the U.S. Food and Drug Administration (FDA) for general medical use. This compound is classified as a histone deacetylase (HDAC) inhibitor, a targeted therapy that interferes with specific enzymes involved in gene expression. As a drug under investigation, its efficacy and safety are being evaluated in clinical trials for various forms of cancer.
How Mocetinostat Works
Within our cells, DNA is a vast library of genetic information that is tightly organized. To fit inside the cell’s nucleus, it is wound around proteins called histones, similar to thread wrapped around a spool. This structure is not static; it can be loosened or tightened to control which genes are active. The tightness of the DNA winding determines whether a gene is turned “on” or “off.” A looser winding allows a gene to be read and activated, while a tighter winding silences it.
Enzymes known as histone deacetylases (HDACs) play a part in this process. HDACs remove specific chemical tags, called acetyl groups, from the histones. This removal causes the DNA to wind more tightly around the histones, effectively turning genes “off.” This mechanism is a normal part of cellular function.
In many cancers, this regulatory system is hijacked. Cancer cells can use HDAC enzymes to silence genes that would normally prevent tumors from growing, known as tumor suppressor genes. By turning these protective genes off, the cancer cells can divide and spread without restraint.
Mocetinostat functions by intervening in this process. As an HDAC inhibitor, it specifically blocks the action of certain HDAC enzymes, including HDAC1, HDAC2, and HDAC3. By inhibiting these enzymes, mocetinostat prevents the removal of the acetyl tags from the histones. This action keeps the DNA in a more relaxed, open state, allowing the previously silenced tumor suppressor genes to be turned back “on.” The reactivation of these genes can restore some of the cell’s natural defenses, leading to the inhibition of cancer cell growth and, in some cases, causing the cancer cells to die.
Cancers Treated by Mocetinostat
Mocetinostat has been investigated in clinical trials for several types of cancer, particularly hematological malignancies and some solid tumors. It has been studied in patients with relapsed or refractory follicular lymphoma, a slow-growing type of non-Hodgkin lymphoma. Favorable results were also announced from a Phase II trial for patients with Hodgkin lymphoma that had returned or was resistant to other treatments.
Another lymphoma subtype where mocetinostat has been evaluated is diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin lymphoma. Research has explored its activity in patients with this disease, often after other therapies have failed.
Beyond lymphomas, mocetinostat has been studied in urothelial carcinoma, the most common type of bladder cancer. Clinical trials have enrolled patients with advanced or metastatic urothelial carcinoma who have previously undergone treatment with platinum-based chemotherapy. Research has also explored its use in other cancers, including myelodysplastic syndromes and leiomyosarcoma, often in combination with other therapeutic agents.
Administration in Clinical Trials
In the context of clinical trials, mocetinostat is administered orally in the form of a capsule. This method of delivery allows for less invasive treatment compared to intravenous therapies.
A common regimen observed in studies involves taking the medication three times a week, such as on Mondays, Wednesdays, and Fridays, rather than daily. This schedule is often part of a 21 or 28-day treatment cycle, which includes periods of rest where the patient does not take the drug.
The dosage itself is also a variable factor. For instance, some trials have started patients at a dose of 70 mg, with the potential to increase to 90 mg if the medication is well-tolerated. Other studies have used different fixed doses or have adjusted the dose based on the patient’s response and any side effects that emerge.
Observed Side Effects
Clinical studies of mocetinostat have documented a range of side effects. These common side effects include:
- Fatigue
- Nausea
- Diarrhea
- Vomiting
- A decreased appetite
More significant side effects have also been observed, primarily affecting the blood. Hematological issues such as thrombocytopenia (a low count of platelets, which help blood clot), neutropenia (a low level of a type of white blood cell that fights infection), and anemia (a low count of red blood cells) have been reported. Patients participating in these trials are monitored closely through regular blood tests to detect these changes early.
In some early trials, cardiac-related issues, specifically pericardial effusion (fluid around the heart) and pericarditis (inflammation of the tissue surrounding the heart), were noted as serious adverse events. This led to a temporary suspension of new patient enrollment in some studies. After review, trials resumed with stricter screening criteria, excluding patients with pre-existing significant heart conditions to enhance safety.