Metformin as a therapeutic tool for resistant hematological malignancies: a literature review

Hematological malignancies (HMs) are a group of neoplasms with hematopoietic origin, currently divided into leukemias, lymphomas and multiple myeloma (MM). Although the advances in the management of HMs, the rate of drug resistance, relapse and refractory disease has been increasing, requiring new therapeutic strategies. In this review, we aim to summarize metformin's antitumoral mechanisms of action and present the latest studies of metformin action in HMs, including in resistant ones.

For this review of literature, studies published between 1996 and 2023 from PubMed and clinical trials submitted to clinicaltrials.gov were considered.

Throughout this review we demonstrated the capacity of metformin to act as an anti-HMs drug, being able to re-sensitize HMs to classical anti-HMs agents and to overcome relapse and refractory HMs, as shown in vitro and in vivo studies. Associated with the potential anti-HM effect of metformin, some clinical trials are in progress, including in the view of reducing resistance and recurrence rate of HMs, which requires further exploration. The relationship among HMs cancer stem cells (HMs CSCs), drug resistance, cancer recurrence, and the effect of metformin in inhibiting CSCs were also discussed, despite this field needing more attention.

In summary, metformin is a promising anti-HMs drug that can enhance patients' survival and prognosis through its action in the improvement of HMs response.