From the Guidelines
MCL1 inhibitors are a promising therapeutic approach for patients with multiple myeloma, particularly those with relapsed or refractory disease, as they target the anti-apoptotic protein MCL-1, which is often overexpressed in this cancer type. According to a study published in Clinical Cancer Research in 2016 1, inhibitors of anti-apoptotic plasma cell proteins such as MCL-1 are considered promising candidates for the treatment of multiple myeloma. The study highlights the need for additional new drugs and new drug classes to be validated to achieve further progress against multiple myeloma.
Some key points to consider when using MCL1 inhibitors in clinical practice include:
- MCL1 inhibitors work by binding to MCL-1, preventing its interaction with pro-apoptotic proteins, thus allowing cancer cells to undergo programmed cell death
- These agents are particularly promising for treating hematologic malignancies like multiple myeloma where MCL1 dependence is high
- Treatment typically involves intravenous administration in clinical trial settings, as these drugs are not yet FDA-approved for standard care
- Side effects may include neutropenia, gastrointestinal symptoms, and cardiac toxicity
- MCL1 inhibitors are often being studied in combination with other targeted therapies like BCL-2 inhibitors to overcome resistance mechanisms
The effectiveness of MCL1 targeting depends on biomarker testing to confirm MCL1 dependence in the specific cancer being treated, as noted in the study 1. Overall, MCL1 inhibitors offer a new therapeutic strategy for patients with multiple myeloma, and their development is an important step towards improving outcomes for these patients.
From the Research
MCL1 Function and Regulation
- MCL1 is an antiapoptotic member of the BCL2 family that regulates cell death, cell cycle progression, and mitochondrial homeostasis 2.
- It has a short half-life and functions as a rapid sensor for these processes 2.
- MCL1 overexpression contributes to cell survival and resistance to chemotherapeutic agents in cancer 2, 3, 4.
MCL1 in Cancer
- MCL1 is frequently overexpressed in many tumor types and is associated with tumorigenesis, poor prognosis, and drug resistance 3, 4, 5.
- Inhibition of MCL1 shows potential as a treatment for hematologic malignancies, including multiple myeloma, acute myeloid leukemia, and non-Hodgkin lymphoma 3.
- Several MCL1 inhibitors are currently under preclinical and clinical development for cancer treatment 2, 3, 4.
MCL1 as a Therapeutic Target
- Targeting MCL1 may complement the activity of BCL-2 inhibitors and enhance anti-tumor efficacy when given in combination with other anti-cancer drugs 3.
- A safe therapeutic window needs to be found for MCL1 inhibitors to avoid potential side effects 3.
- MCL1 expression levels may be used for disease monitoring, as they decrease after complete remission and increase after relapse 5.
- Inhibition of MCL1 expression and/or neutralization of its anti-apoptotic function may provide an opportunity to combat several types of cancers 6.