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

Crucitta, Stefania; Cucchiara, Federico; Mathijssen, Ron H.J.; Mateo, Joaquín; Jager, Agnes; Joosse, Arjen; Passaro, Antonio; Attili, Ilaria; Petrini, Iacopo; Schaik, Ron van; Danesi, Romano; Re, Marzia Del

doi:10.1016/j.ctrv.2022.102340

Cited by 37 publications

(21 citation statements)

References 222 publications

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“…Primary drug resistance is a phenomenon that already exists in tumor diagnosis, and acquired drug resistance is closely related to the selective pressure of treatment. The pharmacological properties of drugs, including their potency, binding affinity, and structural stability, largely influence the mechanisms of drug resistance that emerge during disease progression [ 69 ]. In recent years, more and more pieces of evidence [ 70 ] have shown that miRNAs are closely related to the survival and chemotherapy sensitivity of tumor patients, and the effect of miRNAs is closely related to the regulation of the expression of ABC (ATP-binding cassette) transporters.…”

Section: Resultsmentioning

confidence: 99%

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Wei

Chai

et al. 2022

IJMS

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Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention.

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Section: Resultsmentioning

confidence: 99%

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Wei

Chai

et al. 2022

IJMS

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“…One of the main causes of treatment failure in OSA and many other cancers is chemotherapy drug resistance [ 11 , 12 ]. Tumor adaptability and the trajectory of cancer cell evolution play a major role in treatment evasion and the development of evasion mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…The primary cause of OSA treatment failure is chemoresistance, which has been attributed to tumor adaptability and the trajectory of tumor cell evolution [ 11 , 12 ]. Tumor adaptability is driven by the key hallmarks of tumorigenesis, genomic instability, and compromised regulation of DNA replication and the cell cycle [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Tumor adaptability is driven by the key hallmarks of tumorigenesis, genomic instability, and compromised regulation of DNA replication and the cell cycle [ 11 ]. Genomic instability results in high levels of copy number variation and genotypic, transcriptomic, and phenotypic heterogeneity within cancerous tissues that can promote adaptive mechanisms for resistance to chemotherapy drugs and the production of highly resistant cancer cells [ 11 , 12 ]. In addition, chemotherapy-induced mutations may drive the tumor’s trajectory by selecting for drug-resistant cell populations [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line

Hodge

Miller

Weinman

et al. 2023

Genes

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Osteosarcoma prognosis has remained unchanged for the past three decades. In both humans and canines, treatment is limited to excision, radiation, and chemotherapy. Chemoresistance is the primary cause of treatment failure, and the trajectory of tumor evolution while under selective pressure from treatment is thought to be the major contributing factor in both species. We sought to understand the nature of platinum-based chemotherapy resistance by investigating cells that were subjected to repeated treatment and recovery cycles with increased carboplatin concentrations. Three HMPOS-derived cell lines, two resistant and one naïve, underwent single-cell RNA sequencing to examine transcriptomic perturbation and identify pathways leading to resistance and phenotypic changes. We identified the mechanisms of acquired chemoresistance and inferred the induced cellular trajectory that evolved with repeated exposure. The gene expression patterns indicated that acquired chemoresistance was strongly associated with a process similar to epithelial–mesenchymal transition (EMT), a phenomenon associated with the acquisition of migratory and invasive properties associated with metastatic disease. We conclude that the observed trajectory of tumor adaptability is directly correlated with chemoresistance and the phase of the EMT-like phenotype is directly affected by the level of chemoresistance. We infer that the EMT-like phenotype is a critical component of tumor evolution under treatment pressure and is vital to understanding the mechanisms of chemoresistance and to improving osteosarcoma prognosis.

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“…It is considered that selective therapeutic pressure could facilitate the emergence of new resistance mutations and change of tumor phenotype finally (16). In the present study, we retrospectively analyzed the treatment response of ABC patients after first-line treatment.…”

Section: Discussionmentioning

confidence: 99%

New classification for advanced breast cancer patients experiencing disease progression during salvage treatment: a single-center retrospective cohort study

Wen¹,

Ren²,

Li³

et al. 2022

Ann Transl Med

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Background: Attributed to inter-tumor heterogeneity, the therapeutic effect of salvage treatment is diverse and different malignant lesions might manifest various therapeutic responses among advanced breast cancer (ABC) patients. The present study aimed to explore the influence of the mode of lesion response on the subsequent treatment and to subclassify ABC patients for precise prognosis prediction.Methods: Based on the inclusion and exclusion criteria, ABC patients were retrospectively collected and followed up in the Guangdong Provincial Hospital of Chinese Medicine between 2018 and 2021.The treatment responses of all malignant lesions were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Testing subclassified models were constructed based on different assembly mode of progressed malignant lesions for further classification of ABC patients experiencing disease progression following first-line treatment. Multivariate survival analyses were performed to assess the second-line progression-free survival (PFS) of various subgroups and screen the suitable classification model. The most suitable model was utilized to classify enrolled ABC patients as a heterogeneous progression-disease (Heter-PD) group or homogeneous progression-disease (Hom-PD) group. Univariate analysis and multivariate Cox regression survival analyses were performed to assess the prognostic value of each variable.Results: A total of 70 ABC patients experiencing disease progression after first-line treatment were enrolled into the analyses and underwent median follow-up of 10.36 months. We constructed 3 testing models and Model C (Hom-PD was defined when all the target and non-target lesions were evaluated as progression, with or without new lesions) could further distinguish ABC patients with worse survival. The second-line progression-free survival (PFS) times were significantly different between two groups (11.04 vs.6.07 months, P=0.034). For ABC patients retaining partial medication after disease progression of first-line treatment, the Heter-PD group showed a tendency of better second-line PFS than the Hom-PD group (13.18 vs. 3.61 months, P=0.430).Conclusions: Based on the disease progression mode after first-line treatment, the classification model could classify ABC patients as Hom-PD and Heter-PD subgroups, which manifest distinct prognoses during the sequential treatment. For Heter-PD patients, retainment of partial medication might be a rational choice for second-line therapy.

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

Cited by 37 publications

References 222 publications

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line

New classification for advanced breast cancer patients experiencing disease progression during salvage treatment: a single-center retrospective cohort study

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