Alisertib is an investigational medication belonging to a class of targeted therapies designed to interfere with specific molecules involved in tumor growth and progression. As a pharmaceutical agent, Alisertib is not yet approved by major regulatory bodies, such as the U.S. Food and Drug Administration (FDA). The drug is being evaluated in clinical trials to determine its safety and effectiveness against various aggressive malignancies. This approach represents a shift from traditional chemotherapy toward more precise medical interventions in oncology.
How Alisertib Works in Cancer Cells
The function of Alisertib centers on disrupting the process of cell division, or mitosis, which cancer cells rely on for rapid proliferation. Specifically, the drug acts as a selective inhibitor of a protein called Aurora Kinase A (AKA). AKA is a master regulator that orchestrates the complex steps required for a cell to accurately separate its chromosomes into two new daughter cells.
By binding to and inhibiting AKA, Alisertib prevents the formation of a properly structured spindle apparatus, the cellular machinery responsible for pulling the chromosomes apart. This inhibition leads to severe defects in the mitotic process, including the formation of abnormal spindles and misaligned chromosomes. These catastrophic errors in cell division activate a self-destruct mechanism within the cancer cell, leading to programmed cell death, or apoptosis.
Cancers Targeted in Clinical Trials
Alisertib has been investigated in cancer types characterized by high rates of cell division and an overexpression of the Aurora Kinase A protein. One malignancy where the drug showed early promise is Peripheral T-cell Lymphoma (PTCL), a group of aggressive, rare blood cancers. The rationale for targeting PTCL stems from observations that Aurora A kinase is often upregulated in these aggressive lymphomas. Alisertib was evaluated in a Phase 3 trial for relapsed/refractory PTCL, which demonstrated activity but ultimately failed to show superiority over existing comparator drugs.
Another primary area of focus is extensive-stage Small Cell Lung Cancer (SCLC), an aggressive neuroendocrine tumor with limited treatment options after initial therapy fails. Data from a multi-arm Phase 2 study demonstrated clinical activity for Alisertib in SCLC, supporting its continued investigation. Currently, Alisertib is being studied in an ongoing Phase 2 trial for patients with SCLC whose disease has progressed following platinum-based chemotherapy and immunotherapy. Beyond these two main types, the drug has also shown activity signals in earlier trials involving other solid tumors, including breast cancer, head and neck squamous cell carcinoma, and gastroesophageal adenocarcinoma.
Current Status of Research and Availability
Alisertib remains an investigational agent and is not commercially available outside of controlled clinical research settings. The process of drug development requires a compound to successfully pass through multiple phases of clinical trials—Phase 1 for safety, Phase 2 for efficacy, and Phase 3 for comparative effectiveness—before regulators consider it for approval. While Alisertib has been studied extensively, it has not yet secured the necessary data for full regulatory clearance.
The current research is concentrating heavily on extensive-stage SCLC, where the drug has recently received an Orphan Drug Designation from the FDA. This designation is granted to therapies intended to treat rare diseases, which provides incentives and regulatory support to the developers. The ongoing Phase 2 trial aims to identify specific biological markers that indicate which SCLC patients may benefit most from the treatment. If the results from this study are compelling, the pharmaceutical company plans to discuss the possibility of an accelerated approval pathway with the FDA.
Managing Potential Adverse Effects
As with most cancer treatments, Alisertib is associated with adverse events. The most common and significant adverse events observed in clinical trials involve the suppression of the bone marrow, known as myelosuppression. This suppression frequently manifests as neutropenia, a reduction in infection-fighting white blood cells, which has been reported as a common Grade 3 or 4 event in patients. Other hematological issues include anemia (low red blood cell count) and thrombocytopenia (low platelet count).
Non-blood-related side effects commonly include fatigue. Patients may also experience gastrointestinal disturbances, such as diarrhea, nausea, and inflammation of the mouth lining, known as stomatitis. Hair loss, or alopecia, is another commonly reported event linked to treatment with Alisertib. Management of these adverse effects is handled by the treating oncologist and may involve supportive care, such as transfusions or growth factor injections for low blood counts, and dose modification or temporary interruption of the drug.