What kind of drugs does bortezomib belong to and its therapeutic mechanism?

Bortezomib is a first-in-class proteasome inhibitor drug mainly used to treat multiple myeloma and mantle cell lymphoma. The drug selectively inhibits the function of the 26S proteasome in cells, interferes with the cellular protein degradation process, and then induces tumor cell apoptosis. Unlike traditional chemotherapy, bortezomib does not directly destroy DNA, but "starves" malignant cells from cell metabolism and survival mechanisms, so its mechanism of action is more selective.

The 26S 26Sproteasome system in human cells is mainly responsible for degrading unnecessary or damaged proteins and maintaining intracellular homeostasis. Cancer cells are more dependent on the proteasome due to their active metabolism and frequent mutations. Bortezomib reversibly inhibits the amidase activity of 26S proteasome, leading to key regulatory proteins such as p53, < Abnormal accumulation of span>p27, IκB, etc. triggers cell cycle arrest and initiation of the apoptosis pathway. Especially in multiple myeloma cells, inhibiting the NF-κB signaling pathway is one of its key anti-tumor mechanisms.

The selective effect of bortezomib makes it highly sensitive to tumor cells but has less effect on normal cells, thus showing a good therapeutic window in clinical practice. It can not only induce tumor cell death, but also inhibit the functions of cells in the tumor cell microenvironment that support tumor growth, such as bone marrow stromal cells and osteoblasts. Therefore, bortezomib not only has significant efficacy in patients with myeloma, but also improves the symptoms of bone destruction and prolongs the remission period.

Since its approval by the FDA in 2003, bortezomib has become a first-line drug for the treatment of multiple myeloma. It is often used in combination with dexamethasone, thalidomide, lenalidomide and other drugs to form standard regimens such as VD, VTD, VRD, etc. It has shown a high response rate in both initial treatment and relapsed and refractory myeloma. In recent years, its subcutaneous injection dosage form has further optimized the convenience and tolerability of medication, allowing patients to obtain a better long-term treatment experience. With the deepening of research, bortezomib is also conducting new explorations in the fields of lymphoma, autoimmune diseases and other fields.

Reference materials:https://www.drugs.com/donanemab.html