CD36: a key mediator of resistance to HER2 inhibitors in breast cancer

Feng, William W.; Bang, Scott; Kurokawa, Manabu

doi:10.1080/23723556.2020.1715766

Cited by 10 publications

(16 citation statements)

References 9 publications

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“…These data demonstrate that trastuzumab administration in patients with breast cancer, a treatment according to one report associated with a 34% rate of brain metastasis 5 , results in increased expression of a cell surface marker that we have observed to be a defining transcriptional feature of early-onset breast cancer 6 , a marker whose expression has been associated with enhanced metastasis in mouse models of cancer 7 , and that this increased expression is likely a direct result of treatment with trastuzumab 3 . Though it has been argued that CD36 is up-regulated during acquisition of resistance in response to HER2 inhibition by trastuzumab 8 , we find here that CD36 up-regulation is readily observable in patient tumor following a single administration of trastuzumab, arguing this reflects primary transcriptional effects of trastuzumab as opposed to changes in gene expression observed over a course of treatment (tumor evolution).…”

Section: Discussioncontrasting

confidence: 51%

CD36 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

Mamoor¹

2021

Preprint

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Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified the scavenger receptor CD36 as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. A single dose of trastuzumab was sufficient to result in differential expression of CD36 in the primary tumors of patients with breast cancer, suggesting that transcriptional induction of CD36 is a direct result of trastuzumab administration.

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Section: Discussioncontrasting

confidence: 51%

CD36 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

Mamoor¹

2021

Preprint

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“…The present study found CD36 expression and its prognostic value in multiple cancer types. In addition, the expression of CD36 was significantly associated with current predictors for the efficacy of ICIs [21,22].…”

Section: Discussionmentioning

confidence: 97%

Prognostic and immunological role of CD36: A pan-cancer analysis

Chen¹,

Liao²,

Huang³

et al. 2021

J. Cancer

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CD36 plays a critical role in lipid metabolism, which is closely associated with human immunity. However, the role of CD36 in cancer remains unclear. We performed a pan-cancer analysis to elucidate the potential role of CD36 in cancer by investigating its prognostic value and current predictors for the efficacy of immune checkpoint inhibitors (ICIs) in multiple cancer types. CD36 expression in cancer cell lines, tumor tissue, and their adjacent normal tissues displayed heterogeneity among different cancers. Immunohistochemistry was used to detect CD36 expression and confirmed the results. CD36 expression significantly affects prognosis in the six cancer types. High CD36 expression was marginally associated with poorer prognosis in four of them and improved prognosis in the remaining two types. CD36 expression was significantly correlated with the 6 immune infiltrates in most cancer types. In addition, CD36 gene expression was positively correlated with Stromal score, Immune score, and ESTIMATE score. A total of 47 immune checkpoint genes were collected and their relationship with CD36 expression was analyzed. CD36 expression was significantly associated with multiple stimulatory and inhibitory checkpoint molecules with a disease-specific pattern. As to the genes reported to positively relate to the efficacy of ICIs, CD36 expression was positively correlated with most of them but negatively associated with a small proportion of cancer type-specific patterns. Concerning the genes negatively related to the efficacy of ICIs, CD36 expression was positively correlated with NRP1 and TNFSF15 in multiple cancers. CD36 expression was negatively correlated with tumor neoantigen burden in most cancer types. However, CD36 expression was negatively correlated with tumor mutation burden in most cancer types. The correlation between CD36 expression and the four methyltransferases was also significant in multiple cancers, but also with a cancer type-specific pattern. In summary, the current study found CD36 expression and its prognostic value in multiple cancer types. In addition, the expression of CD36 was significantly associated with current predictors for the efficacy of ICIs. The practical application value of CD36 is disease specific.

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“…Vazquez-Martin et al [ 110 ] reported that the FASN-mediated FAs de novo biosynthesis is inhibited in response to HER2 inhibition and cancer cells undergo apoptosis, indicating crosstalk between FASN and HER2. However, a recent study found that lapatinib-resistant cells are unresponsive to (-)-C75, which is well-established to suppress FASN [ 111 ] . Furthermore, the lapatinib-resistant cells showed a significantly higher level of CD36 with an enhanced rate of FAs uptake, as well as an increase in the presence of lipid droplets compared to their sensitive counterparts [ 112 ] .…”

Section: Specific Mechanisms Of Resistancementioning

confidence: 99%

An overview of resistance to Human epidermal growth factor receptor 2 (Her2) targeted therapies in breast cancer

Elshazly¹,

Gewirtz²

2022

Cancer Drug Resist

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Breast cancer (BC) is the second most common cause of cancer-related deaths and the most frequently diagnosed cancer in females. Among breast cancer types, HER2-positive breast cancer occurs in nearly 20% of human breast cancers and is associated with increased aggressiveness, poor prognosis, and shortened overall survival. HER2+ breast cancer is currently managed with multidisciplinary treatment strategies including surgery, radiation, chemotherapy, and targeted therapy. Drug resistance remains a continuing challenge, especially to targeted therapy utilizing monoclonal antibodies and tyrosine kinase inhibitors. This review discusses some of the recent molecular mechanisms that are involved in the development of resistance to Her2-targeted therapies including the PI3K/Akt/mTOR pathway, IGF-IR, Src, c-MET, the PP2A family, CD36, p27kip1, and miRNAs.

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CD36: a key mediator of resistance to HER2 inhibitors in breast cancer

Cited by 10 publications

References 9 publications

CD36 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

CD36 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

Prognostic and immunological role of CD36: A pan-cancer analysis

An overview of resistance to Human epidermal growth factor receptor 2 (Her2) targeted therapies in breast cancer

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