Mechanisms of lapatinib resistance in HER2-driven breast cancer

Damato, Valentina; Raimondo, Lucia; Formisano, Luigi; Giuliano, Mario; Placido, Sabino De; Rosa, Roberta; Bianco, Roberto

doi:10.1016/j.ctrv.2015.08.001

Cited by 130 publications

(120 citation statements)

References 55 publications

(70 reference statements)

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“…Whereas, TKIs function by inhibiting the cytosolic tyrosine kinase domains through either direct competition with ATP or allosteric inhibition of ATP binding (Levitzki and Mishani, 2006). While both of these therapeutic strategies have had promising results in both the pre-clinical setting as well as in clinical trials, innate and acquired resistance has presented itself as a key challenge for both types of therapies (Nguyen et al, 2009; Oxnard et al, 2011; Stern, 2012; Arteaga and Engelman, 2014; Creedon et al, 2014; D'Amato et al, 2015; Forde and Ettinger, 2015; Landi and Cappuzzo, 2015; Gollamudi et al, 2016; Luque-Cabal et al, 2016). …”

Section: Therapeutic Targetingmentioning

confidence: 99%

“…The dual-targeting TKI Lapatinib, which inhibits both EGFR and ErbB2, is approved for use in ErbB2 positive breast cancer upon relapse following treatment standard chemotherapy and trastuzumab (Nolting et al, 2014). Although, a number of different mechanisms of both acquired and innate resistance to lapatinib have been identified, including compensatory signaling, mutation of ErbB2 and reactivation of the estrogen receptor pathway (D'Amato et al, 2015). …”

Section: Therapeutic Targetingmentioning

confidence: 99%

“…Attempts to address this common theme of resistance toward EGFR-family targeted therapies has been met with only partial success (Creedon et al, 2014; D'Amato et al, 2015), indicating that our understanding of acquired resistance in this context is not sufficiently developed. Acquired resistance to EGFR family targeted therapies has been variously attributed to a change in receptor expression or structure, the development of alternative means of activating survival and proliferation pathways governed by the EGFR family, and by a shift in dimerization profile of these receptors (Sergina et al, 2007; Stern, 2012; Arteaga and Engelman, 2014; Creedon et al, 2014; Luque-Cabal et al, 2016).…”

Section: Therapeutic Targetingmentioning

confidence: 99%

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The Under-Appreciated Promiscuity of the Epidermal Growth Factor Receptor Family

Kennedy

Hastings

Han

et al. 2016

Front. Cell Dev. Biol.

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Each member of the epidermal growth factor receptor (EGFR) family plays a key role in normal development, homeostasis, and a variety of pathophysiological conditions, most notably in cancer. According to the prevailing dogma, these four receptor tyrosine kinases (RTKs; EGFR, ERBB2, ERBB3, and ERBB4) function exclusively through the formation of homodimers and heterodimers within the EGFR family. These combinatorial receptor interactions are known to generate increased interactome diversity and therefore influence signaling output, subcellular localization and function of the heterodimer. This molecular plasticity is also thought to play a role in the development of resistance toward targeted cancer therapies aimed at these known oncogenes. Interestingly, many studies now challenge this dogma and suggest that the potential for EGFR family receptors to interact with more distantly related RTKs is much greater than currently appreciated. Here we discuss how the promiscuity of these oncogenic receptors may lead to the formation of many unexpected receptor pairings and the significant implications for the efficiency of many targeted cancer therapies.

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Section: Therapeutic Targetingmentioning

confidence: 99%

Section: Therapeutic Targetingmentioning

confidence: 99%

Section: Therapeutic Targetingmentioning

confidence: 99%

See 1 more Smart Citation

The Under-Appreciated Promiscuity of the Epidermal Growth Factor Receptor Family

Kennedy

Hastings

Han

et al. 2016

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Further, lapatinib is introduced to overcome all of the resistance phenomena. Lapatinib effectively works both on tyrosine kinase EGFR and HER2 as well as ER receptor (D'Amato et al, 2015). The finding of lapatinib becomes a new insight to develop a chemotherapeutic targeted as a dual inhibitor not only targeted to the HER2 receptor but also EGFR.…”

mentioning

confidence: 99%

“…The finding of lapatinib becomes a new insight to develop a chemotherapeutic targeted as a dual inhibitor not only targeted to the HER2 receptor but also EGFR. Recently, several cases reported that some patients were resistant to lapatinib treatment (D'Amato et al, 2015). Therefore, development of an ideal chemotherapeutic agent targeted on both EGFR and HER2 receptor needs to be explored thoroughly.…”

mentioning

confidence: 99%

Synthesis and Cytotoxic Activity of 2,5-Bis(4-Boronic Acid)benzylidine Cyclopentanone on Her2 Overexpressed-Cancer Cells

Utomo¹,

Putri²,

Pudjono³

et al. 2017

Indonesian J. Pharm.

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Development of chemotherapeutic agent and boron carrying pharmaceutical based on HER2 specific targeted is important due to its role in enhancing cancer progression. The purpose of this study is to synthesize curcumin analogue, namely Pentagamaboron-0 (PGB-0) or 2,5-bis(4-boronic acid)benzylidine cyclopentanone, and to explore the cytotoxic activity on HER2 overexpressed-cancer cells. MCF-7/HER2 was used as a model of HER2 overexpressed-cancer cells and NIH3T3 as normal cells. PGB-0 bound to ATP binding site of HER2 and EGFR based on molecular docking study. PGB-0 was synthesized resulting in 33% yield and was confirmed by IR, 1 HNMR, 13 CNMR and Mass spectroscopy. Based on MTT assay PGB-0 decreased cells viability on MCF-7/HER2 cells with IC 50 value of 270µM but performed no effect on NIH3T3 cells. Cell cycle analysis revealed that PGB-0 increased sub-G1 accumulation. PGB-0 decreased HER2 expression in a dose-dependent manner. We conclude that the new compound PGB-0 inhibits cell growth through cell death induction and decreased HER2 expression. Thus, PGB-0 is potential to be developed as a chemotherapeutic agent and boron carrying pharmaceutical targeted on the HER2 receptor.

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Enantioselective Synthesis of Quinazoline‐Based Heterocycles through Phosphine‐Catalyzed Asymmetric [3+3] Annulation of Morita−Baylis−Hillman Carbonates with Azomethine Imines

et al. 2017

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Enantioselective synthesis of chiral quinazoline‐based heterocycles is achieved through a chiral phosphine‐catalyzed [3+3] annulation reaction of quinazoline‐based 1,3‐dipoles with Morita−Baylis−Hillman carbonates. The reaction proceeds smoothly under mild conditions to give various chiral heterocyclic compounds in high yields with excellent diastereoselectivities and enantioselectivities. Further diverse elaborations of the annulation products work well to produce novel tetrahydroquinazoline derivatives.magnified image

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Mechanisms of lapatinib resistance in HER2-driven breast cancer

Cited by 130 publications

References 55 publications

The Under-Appreciated Promiscuity of the Epidermal Growth Factor Receptor Family

The Under-Appreciated Promiscuity of the Epidermal Growth Factor Receptor Family

Synthesis and Cytotoxic Activity of 2,5-Bis(4-Boronic Acid)benzylidine Cyclopentanone on Her2 Overexpressed-Cancer Cells

Enantioselective Synthesis of Quinazoline‐Based Heterocycles through Phosphine‐Catalyzed Asymmetric [3+3] Annulation of Morita−Baylis−Hillman Carbonates with Azomethine Imines

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