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CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review

The cyclin D-CDK4/6 complexes play a pivotal role in controlling the cell cycle. Deregulation in cyclin D-CDK4/6 pathway has been described in many types of cancer and it invariably leads to uncontrolled cell proliferation. Many efforts have been made to develop a target therapy able to inhibit CDK4...

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Autores principales: Rampioni Vinciguerra, Gian Luca, Sonego, Maura, Segatto, Ilenia, Dall’Acqua, Alessandra, Vecchione, Andrea, Baldassarre, Gustavo, Belletti, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197541/
https://www.ncbi.nlm.nih.gov/pubmed/35712501
http://dx.doi.org/10.3389/fonc.2022.891580
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author Rampioni Vinciguerra, Gian Luca
Sonego, Maura
Segatto, Ilenia
Dall’Acqua, Alessandra
Vecchione, Andrea
Baldassarre, Gustavo
Belletti, Barbara
author_facet Rampioni Vinciguerra, Gian Luca
Sonego, Maura
Segatto, Ilenia
Dall’Acqua, Alessandra
Vecchione, Andrea
Baldassarre, Gustavo
Belletti, Barbara
author_sort Rampioni Vinciguerra, Gian Luca
collection PubMed
description The cyclin D-CDK4/6 complexes play a pivotal role in controlling the cell cycle. Deregulation in cyclin D-CDK4/6 pathway has been described in many types of cancer and it invariably leads to uncontrolled cell proliferation. Many efforts have been made to develop a target therapy able to inhibit CDK4/6 activity. To date, three selective CDK4/6 small inhibitors have been introduced in the clinic for the treatment of hormone positive advanced breast cancer patients, following the impressive results obtained in phase III clinical trials. However, since their approval, clinical evidences have demonstrated that about 30% of breast cancer is intrinsically resistant to CDK4/6 inhibitors and that prolonged treatment eventually leads to acquired resistance in many patients. So, on one hand, clinical and preclinical studies fully support to go beyond breast cancer and expand the use of CDK4/6 inhibitors in other tumor types; on the other hand, the question of primary and secondary resistance has to be taken into account, since it is now very clear that neoplastic cells rapidly develop adaptive strategies under treatment, eventually resulting in disease progression. Resistance mechanisms so far discovered involve both cell-cycle and non-cell-cycle related escape strategies. Full understanding is yet to be achieved but many different pathways that, if targeted, may lead to reversion of the resistant phenotype, have been already elucidated. Here, we aim to summarize the knowledge in this field, focusing on predictive biomarkers, to recognize intrinsically resistant tumors, and therapeutic strategies, to overcome acquired resistance.
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spelling pubmed-91975412022-06-15 CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review Rampioni Vinciguerra, Gian Luca Sonego, Maura Segatto, Ilenia Dall’Acqua, Alessandra Vecchione, Andrea Baldassarre, Gustavo Belletti, Barbara Front Oncol Oncology The cyclin D-CDK4/6 complexes play a pivotal role in controlling the cell cycle. Deregulation in cyclin D-CDK4/6 pathway has been described in many types of cancer and it invariably leads to uncontrolled cell proliferation. Many efforts have been made to develop a target therapy able to inhibit CDK4/6 activity. To date, three selective CDK4/6 small inhibitors have been introduced in the clinic for the treatment of hormone positive advanced breast cancer patients, following the impressive results obtained in phase III clinical trials. However, since their approval, clinical evidences have demonstrated that about 30% of breast cancer is intrinsically resistant to CDK4/6 inhibitors and that prolonged treatment eventually leads to acquired resistance in many patients. So, on one hand, clinical and preclinical studies fully support to go beyond breast cancer and expand the use of CDK4/6 inhibitors in other tumor types; on the other hand, the question of primary and secondary resistance has to be taken into account, since it is now very clear that neoplastic cells rapidly develop adaptive strategies under treatment, eventually resulting in disease progression. Resistance mechanisms so far discovered involve both cell-cycle and non-cell-cycle related escape strategies. Full understanding is yet to be achieved but many different pathways that, if targeted, may lead to reversion of the resistant phenotype, have been already elucidated. Here, we aim to summarize the knowledge in this field, focusing on predictive biomarkers, to recognize intrinsically resistant tumors, and therapeutic strategies, to overcome acquired resistance. Frontiers Media S.A. 2022-05-27 /pmc/articles/PMC9197541/ /pubmed/35712501 http://dx.doi.org/10.3389/fonc.2022.891580 Text en Copyright © 2022 Rampioni Vinciguerra, Sonego, Segatto, Dall’Acqua, Vecchione, Baldassarre and Belletti https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Rampioni Vinciguerra, Gian Luca
Sonego, Maura
Segatto, Ilenia
Dall’Acqua, Alessandra
Vecchione, Andrea
Baldassarre, Gustavo
Belletti, Barbara
CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review
title CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review
title_full CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review
title_fullStr CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review
title_full_unstemmed CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review
title_short CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review
title_sort cdk4/6 inhibitors in combination therapies: better in company than alone: a mini review
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197541/
https://www.ncbi.nlm.nih.gov/pubmed/35712501
http://dx.doi.org/10.3389/fonc.2022.891580
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