Polytherapy and Targeted Cancer Drug Resistance

Chatterjee, Nilanjana; Bivona, Trever G.

doi:10.1016/j.trecan.2019.02.003

Cited by 214 publications

(157 citation statements)

References 141 publications

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“…In order to overcome CDR, some therapeutic strategies suggest the intermittent management of cancer drugs, whereupon drugs are applied in time cycles to prevent acquired resistance [33,34]. However, as acquired CDR is a time-dependent process, the assessment of the mechanisms that are activated as cells to develop resistance is critical.…”

Section: Discussionmentioning

confidence: 99%

ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance

Gomes

Honrado

Armada

et al. 2020

IJMS

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Cancer drug resistance (CDR) is a major problem in therapeutic failure. Over 90% of patients with metastatic cancer present CDR. Several mechanisms underlie CDR, including the increased expression of efflux ABC transporters and epigenetic phenomena. Nevertheless, a topic that is not usually addressed is the mechanism underlying the loss of CDR once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant, expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium. ABCB1 activity was analysed by fluorescence microscopy and flow cytometry through substrate (DiOC2) retention assays. The expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal, a decrease of ABCB1 activity and expression occurred. Moreover, we determined a signature of 23 microRNAs, 13 underexpressed and 10 overexpressed, as a tool to assess loss of resistance. Through pathway enrichment analysis, "Pathways in cancer", "Proteoglycans in cancer" and "ECM-receptor interaction" were identified as relevant in the loss of CDR. Taken together, the data reinforce the assumption that ABCB1 plays a major role in the kinetics of CDR, and their levels of expression are in the dependence of the circuitry of cell miRNAs.

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Section: Discussionmentioning

confidence: 99%

ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance

Gomes

Honrado

Armada

et al. 2020

IJMS

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“…Breast cancer has been the highest incidence of cancer among women (Torre et al, 2015;Chen et al, 2018). However, the current therapeutic methods, including hormone therapy, radiotherapy, surgery, and chemotherapy, are not satisfied due to the accompanied side effect and multiple drug resistance (Peng et al, 2009;Akram et al, 2017;Chatterjee & Bivona, 2019), which will in return aggravate the patient's depression (Rao et al, 2019), the most widely occurred symptom among the breast cancer patients (Zainal et al, 2013;Shah et al, 2014;Stanton & Bower, 2015).…”

Section: Introductionmentioning

confidence: 99%

Hydrous icaritin nanorods with excellent stability improves the in vitro and in vivo activity against breast cancer

Wang

Huang

et al. 2020

Drug Delivery

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Due to their various biological activities that are beneficial to human health and antitumor effect, flavonoid compounds have attracted much attention in recent years. Hydrous icaritin (HICT) was such a flavonoid that can inhibit the growth of breast cancer and cancer stem cells. In order to overcome the insolubility problem, HICT was fabricated into nanorods (NRs) through anti-solvent precipitation in this paper using D-a tocopherol acid polyethylene glycol succinate and sodium oleate as a co-stabilizer meanwhile using the mixture of ethanol and acetone (1:2, v/v) as the organic solvent. The obtained HICT NRs showed an average particle size 222.0 nm with a small polydispersity index value of 0.124 and a high zeta potential of-49.5 mV. HICT NRs could maintain similar particle size in various physiological medium and could be directly lyophilized without the addition of any cytoprotectants and then reconstituted into a colloidal system of similar size. The resultant HICT NRs had a high drug loading content of 55.6% and released HICT in a steady and constant pattern. MTT assay indicated NRs enhanced HICT's antitumor activity to ninefold against MCF-7 breast carcinoma cells. In vivo studies demonstrated oral administration free HICT had almost no tumor inhibitory effect while HICT NRs showed a tumor inhibition rate of 47.8%. When intravenously injected, HICT NRs displayed similar therapeutic efficacy to paclitaxel injections (70.4% vs. 74.5%, TIR). This may be partly due to the high accumulation of the injected HICT NRs in tumor ranking only second to that in the liver but much higher than in other organs. These results demonstrated that HICT NRs could be a promising antitumor agent for the treatment of breast cancer in clinic.

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“…Nevertheless, drug-tolerant cell clones can proliferate and potentially hijack tumor evolution generating resistant phenotypes. Future perspectives should take in consideration also alternative strategies in order to prevent these phenomena: safe combination of drugs (given together or as switching therapies) targeting different signalling pathways; intermitting administrations which may control tumor heterogeneity and development of resistant clones; reprogramming agents (e.g., epigenetic modifiers) able to interfere with tumor cells adaptation and tumorstroma interaction (67,68) (Figure 1).…”

Section: Biological Challenges Of Adjuvant Therapymentioning

confidence: 99%

Expanding anaplastic lymphoma kinase therapeutic indication to early stage non-small cell lung cancer

Tabbò

Novello

2019

Transl. Lung Cancer Res.

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Oncogene-addicted non-small cell lung cancer (NSCLC) patients have been witnessing overwhelming therapeutic improvements, especially in advanced disease management, due to the advent of more potent tyrosine kinase inhibitors (TKIs). However, the concrete chance to cure anaplastic lymphoma kinase (ALK)-rearranged patients remains prerogative of surgical and peri-operative medical approaches to early disease stage. Clinical investigations in the adjuvant setting of genotype-restricted lung cancers (i.e., EGFR+, ALK+, etc.) are under-represented owing to the need of large patients' enrollment and solid overall survival (OS) data, which solely can show real long-term impact of these therapeutic interventions. Current available radiological and molecular technologies will widely increase the number of surgical early stage patients, including ALK+, spurring the development of rational approaches aimed to prevent disease recurrence and prolong patients' survival. Ongoing clinical trials, evaluating crizotinib and alectinib as adjuvant treatments, will gauge the real impact of TKIs in terms of patients' disease free survival (DFS) and OS; other peri-operative investigations (e.g., neo-adjuvant strategies) will add information about ALK inhibitors' tumor growth restraint capacities and early adaptation mechanisms to ALK targeting. Nevertheless, multiple questions are and will remain unanswered: if should be treated indifferently all ALK+ patients or, alternatively, should be stratified in different risk groups based on the detectable residual disease [i.e., minimal residual disease (MRD) after surgery]; whether ALK inhibitors administration could facilitate the accumulations of persister cells driving resistance mechanisms to targeted therapies; if alternative strategies, as combined treatments targeting different molecular hubs, could enhance disease control and cancer eradication.

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Polytherapy and Targeted Cancer Drug Resistance

Cited by 214 publications

References 141 publications

ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance

ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance

Hydrous icaritin nanorods with excellent stability improves the in vitro and in vivo activity against breast cancer

Expanding anaplastic lymphoma kinase therapeutic indication to early stage non-small cell lung cancer

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