Treatment-driven tumour heterogeneity and drug resistance: Lessons from solid tumours

Stefania Crucitta, Federico Cucchiara, Ron Mathijssen, Joaquin Mateo, Agnes Jager, Arjen Joosse, Antonio Passaro, Ilaria Attili, Iacopo Petrini, Ron van Schaik, Romano Danesi*, Marzia Del Re

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

26 Citations (Scopus)


Molecular heterogeneity characterizes tumours’ evolution and adaptation and, because of its dynamics and continuous changes under external pressure, it is one of the major causes of drug resistance, contributing to therapy failure. Several studies reported evidence of molecular events occuring in individual tumours, including monoclonal or polyclonal resistance, and primary or secondary resistance mechanisms. While primary resistance is a phenomenon already present at the diagnosis of a tumor, the acquired one is strongly related to the selective pressure of treatments administered. Therefore, the pharmacological characteristics of a drug, including its potency, binding affinity and structure, largely influence the mechanism of resistance that will arise at the progression of the disease. As an example, the lung cancer experience clearly demonstrated that the highest is the potency of a drug on its target, the more are the possibilities that the mechanism of resistance will arise independently of the target itself. The present review is focused on tumour heterogeneity and its relation to resistance to targeted-therapy, based on treatment selective pressure across different tumour types, including lung, colorectal, prostate, breast cancer and melanoma. The mechanisms of resistance based on the drug potency and the selective pressure of treatments are discussed, leading to new drug developments or new therapeutic combinations.

Original languageEnglish
Article number102340
JournalCancer Treatment Reviews
Publication statusPublished - Mar 2022

Bibliographical note

Funding Information:
None. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Publisher Copyright:
© 2022 Elsevier Ltd


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