Alisertib is an investigational drug that belongs to a class of compounds known as small molecule inhibitors. It is currently being studied in clinical trials to understand its effects and how it might benefit patients. This compound represents a targeted approach in cancer therapy, focusing on specific molecular pathways involved in tumor growth. The ongoing research aims to determine its effectiveness, appropriate dosages, and safety profile.
What Alisertib Is and How It Works
Alisertib, also known by its research designation MLN8237, is an orally available, selective small molecule inhibitor. It specifically targets and inhibits Aurora A kinase, an enzyme that plays a significant role in cell division.
The inhibition of Aurora A kinase by alisertib disrupts the normal process of mitosis, which is how cells divide. This disruption can lead to several defects in cancer cells, including abnormal formation of the mitotic spindle, which is essential for separating chromosomes correctly. As a result, cancer cells may experience delayed entry into and progression through mitosis, leading to an accumulation of cells with an abnormal number of chromosomes, or tetraploidy. These cellular abnormalities can trigger programmed cell death, known as apoptosis, or cause cells to exit mitosis without fully dividing, a process called mitotic slippage, ultimately hindering tumor growth.
Cancers Studied with Alisertib
Alisertib has been, and continues to be, investigated in various cancer types through clinical trials. Its application is primarily within a research context, exploring its efficacy as a single agent or in combination with other therapies. Studies have explored its use in both solid tumors and hematologic (blood) malignancies.
Specific cancers where alisertib has been evaluated include breast cancer, such as metastatic estrogen receptor-positive (ER-positive) HER2-negative breast cancer and triple-negative breast cancer. It has also been studied in small cell lung cancer, head and neck cancer, and ovarian cancer. Furthermore, alisertib has shown promise in certain lymphomas, including peripheral T-cell lymphoma (PTCL) and aggressive non-Hodgkin lymphomas, as well as in acute myeloid leukemia and neuroblastoma. Clinical trials have also investigated alisertib in various sarcomas, including liposarcoma and leiomyosarcoma, and in urothelial cancer.
Understanding Potential Side Effects
Alisertib can cause various side effects, which are carefully monitored in clinical trials. Patients receiving alisertib are under close medical supervision to manage these potential effects.
Common side effects associated with alisertib often include issues related to the gastrointestinal system, such as nausea, diarrhea, and mucositis, which is inflammation of the mucous membranes in the mouth and digestive tract. Fatigue is another frequently reported side effect. Myelosuppression, a reduction in bone marrow activity, can lead to decreased blood cell counts, specifically neutropenia (low white blood cells, increasing infection risk), leukopenia (low total white blood cells), and anemia (low red blood cells, causing tiredness and breathlessness). Other reported side effects include hair loss (alopecia), high temperature, constipation, dizziness, itching, swelling due to fluid buildup (oedema), cough, and nosebleeds.
Current Status and Future Directions
Alisertib’s development continues through various phases of clinical trials. The global rights for its research and commercialization were licensed by Puma Biotechnology from Takeda in 2022. This agreement signifies ongoing efforts to advance alisertib, particularly with an initial focus on metastatic estrogen receptor-positive HER2-negative breast cancer, triple-negative breast cancer, and small cell lung cancer.
Ongoing research includes active studies combining alisertib with other approved cancer drugs, such as irinotecan and temozolomide for neuroblastoma, and with paclitaxel for small cell lung cancer. While some single-agent studies, like those in ovarian cancer, did not show sufficient activity for further monotherapy development, alisertib’s manageable toxicity profile suggests its potential in combination therapies. Its future development aims to explore its therapeutic potential across a broader range of malignancies.