Key regulators of sensitivity to immunomodulatory drugs in cancer treatment

Abstract

Immunomodulatory drugs (IMiDs) include thalidomide, lenalidomide, and pomalidomide, which have shown significant efficacy in the treatment of multiple myeloma (MM), myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) and other hematological malignancies. IMiDs hijack the CRL4CRBN ubiquitin ligase to target cellular proteins for ubiquitination and degradation, which is responsible for their clinical activity in MM and MDS with del(5q). However, intrinsic and acquired resistance frequently limit the efficacy of IMiDs. Recently, many efforts have been made to explore key regulators of IMiD sensitivity, resulting in great advances in the understanding of the regulatory networks related to this class of drugs. In this review, we describe the mechanism of IMiDs in cancer treatment and summarize the key regulators of IMiD sensitivity. Furthermore, we introduce genome-wide CRISPR-Cas9 screenings, through which the regulatory networks of IMiD sensitivity could be identified.

Síndrome Mielodisplásico por deleción del brazo largo del cromosoma 5. Reporte de caso y revisión de la literatura – myelodysysplasic

“…Wang S, et al (13). Apoya la idea anterior demostrando que existe desregularización de las vías Wnt/B-catenina, IL-6/STAT3 y MEK/ERK y mutaciones de CRBN, IKZF1, entre otros ligándolos al mecanismo de resistencia al tratamiento con lenalidomida, promoviendo el uso de quimeras dirigidas a proteólisis (PROTAC) que permiten combatir a la tumorigénesis de esta patología.…”

Pan-cancer analysis reveals the prognostic and immunologic roles of cereblon and its significance for PROTAC design

“…Drug design based on CRBN have developed rapidly. IMiDs have shown potent efficacy and become one of the standard approaches in hematological malignancies, the regulatory networks of this class of drugs are being explored [ 38 ]. In gastrointestinal cancer, a novel CRBN E3 ligase modulator called MDEG-541 was developed.…”

Electrical Stimulation for Immune Modulation in Cancer Treatments

“…types of cancers (Murahata and Mitchell, 1976;Pettenati and Ingersoll, 2018). Lastly, immunomodulatory drugs that modify biological responses are also used for cancer therapies (Piccolomo et al, 2020;Wang et al, 2021).…”

“…Apart from that, BCG or Bacillus Calmette-Guérin is used broadly for treatment of gut cancer and a few other types of cancers ( Murahata and Mitchell, 1976 ; Pettenati and Ingersoll, 2018 ). Lastly, immunomodulatory drugs that modify biological responses are also used for cancer therapies ( Piccolomo et al, 2020 ; Wang et al, 2021 ).…”