Overcoming trastuzumab resistance in HER2‐positive breast cancer using combination therapy

Derakhshani, Afshin; Rezaei, Zohreh; Safarpour, Hossein; Sabri, Morteza; Mir, Atefeh; Sanati, Mohammad Amin; Vahidian, Fatemeh; Moghadam, Ali Gholamiyan; Aghadoukht, Ali; Hajiasgharzadeh, Khalil; Baradaran, Behzad

doi:10.1002/jcp.29216

Cited by 90 publications

(66 citation statements)

References 117 publications

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“…With the exception of trastuzumab's unmatched beneficial effect for HER-2 positive patients [95], traditionally, toxic and unspecific chemotherapy is used to treat ER negative tumors. In addition, a caveat to the success of trastuzumab for HER-2 positive breast cancer is that a large majority of those treated develop resistance over time [96]. This highlights the need for targeted therapies which can mimic the wide reaching success of anti-estrogens such as tamoxifen for ER positive cancers [97].…”

Section: Discussionmentioning

confidence: 99%

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Mahdi

Malacrida

Nolan

et al. 2020

Cells

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When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.

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Section: Discussionmentioning

confidence: 99%

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Mahdi

Malacrida

Nolan

et al. 2020

Cells

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“…Apart from nanotechnology, drug combination therapy aiming at synergies, resistance reduction and rejuvenation of old drugs, is another approach showing increasing benefits in the treatment of several diseases, particularly cancer [30,31] and bacterial infections [32]. In experimental schistosomiasis, promising results have been reported for combinations involving PZQ and other drugs or biomolecules, aiming at multistage targeting, amelioration of infection-associated pathologies and resistance reduction [12,14].…”

Section: Introductionmentioning

confidence: 99%

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

et al. 2020

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Background The control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed-dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy. Methods Two nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed-dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed-dose), respectively. Their antischistosomal efficacy in comparison with a non-treated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, and on days 21 and 42 post-infection. Scanning electron microscopic, parasitological, and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukeyʼs post-hoc test for pairwise comparisons. Results Lipid nanocapsules (~ 58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher nanocombination dose showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron microscopy examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures. Conclusions The therapeutic profile of praziquantel could be improved by a novel multiple approach integrating drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed-dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed-dose nano-based combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components.

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“…On the other hand, numerous chemotherapeutic drugs or radiotherapy exert their cytotoxic impacts through the increased apoptosis response, and this apoptosis was commonly believed to be non-inflammatory and non-immunogenic. Moreover, antigen-specific T-cell immunity is commonly shown to be induced as a result of danger signals emitted by cells treated by chemotherapeutic drugs including oxaliplatin or radiotherapy [220,221]. If various chemotherapeutic agents are applied, a variety of DAMPs can mediate antitumor immunity; though the overall outcome is determined by the induction of immunogenic cancer cell death and the acquisition of tumor antigens by APCs once tumor-specific killer T cell response is elicited [93].…”

Section: Therapies Combining Chemotherapy-induced Icdmentioning

confidence: 99%

Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death

Asadzadeh

Safarzadeh

Safaei

et al. 2020

Cancers

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117

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Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.

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Overcoming trastuzumab resistance in HER2‐positive breast cancer using combination therapy

Cited by 90 publications

References 117 publications

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death

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