Ca2+ and CACNA1H mediate targeted suppression of breast cancer brain metastasis by AM RF EMF
Abstract
BACKGROUND: Brain metastases are a major cause of death in patients with metastatic breast cancer. While surgical resection and radiation therapy are effective treatment modalities, the majority of patients will succumb from disease progression. We have developed a novel therapy for brain metastases that delivers athermal radiofrequency electromagnetic fields that are amplitude-modulated at breast cancer specific frequencies (BCF). METHODS: 27.12 MHz amplitude-modulated BCF were administered to a patient with a breast cancer brain metastasis by placing a spoon-shaped antenna on the anterior part of the tongue for three one-hour treatments every day. In preclinical models, a BCF dose, equivalent to that delivered to the patient's brain, was administered to animals implanted with either brain metastasis patient derived xenografts (PDXs) or brain-tropic cell lines. We also examined the efficacy of combining radiation therapy with BCF treatment. Additionally, the mechanistic underpinnings associated with cancer inhibition was identified using an agnostic approach. FINDINGS: Animal studies demonstrated a significant decrease in growth and metastases of brain-tropic cell lines. Moreover, BCF treatment of PDXs established from patients with brain metastases showed strong suppression of their growth ability. Importantly, BCF treatment led to significant and durable regression of brain metastasis of a patient with triple negative breast cancer. The tumour inhibitory effect was mediated by Ca influx in cancer cells through CACNA1H T-type voltage-gated calcium channels, which, acting as the cellular antenna for BCF, activated CAMKII/p38 MAPK signalling and inhibited cancer stem cells through suppression of β-catenin/HMGA2 signalling. Furthermore, BCF treatment downregulated exosomal miR-1246 level, which in turn decreased angiogenesis in brain environment. Therefore, targeted growth inhibition of breast cancer metastases was achieved through CACNA1H. INTERPRETATION: We demonstrate that BCF, as a single agent or in combination with radiation, is a novel treatment approach to the treatment of brain metastases. This paradigm shifting modality warrants further clinical trials for this unmet medical need.
AI evidence extraction
Main findings
27.12 MHz athermal amplitude-modulated RF EMF at breast cancer specific frequencies was associated with decreased growth/metastases in brain-tropic cell line animal models and strong suppression of growth in brain metastasis PDX models. The authors report significant and durable regression of a brain metastasis in one patient, and propose mediation via Ca2+ influx through CACNA1H with downstream signaling changes and reduced angiogenesis-related markers.
Outcomes measured
- Tumor growth and metastases in animal models
- Growth suppression of patient-derived xenografts (PDXs) from brain metastases
- Clinical regression of brain metastasis in a patient with triple negative breast cancer
- Mechanistic endpoints: Ca2+ influx via CACNA1H T-type channels; CAMKII/p38 MAPK signaling; suppression of β-catenin/HMGA2 signaling; cancer stem cell inhibition; exosomal miR-1246 downregulation; angiogenesis in brain environment
- Efficacy in combination with radiation therapy (mentioned)
Limitations
- Clinical evidence described for a single patient; broader clinical sample size not provided in abstract
- Animal study details (numbers, randomization/blinding) not provided in abstract
- Exposure dosimetry (e.g., SAR) not reported in abstract
View raw extracted JSON
{
"study_type": "other",
"exposure": {
"band": "RF",
"source": "therapeutic device (spoon-shaped antenna on tongue)",
"frequency_mhz": 27.120000000000000994759830064140260219573974609375,
"sar_wkg": null,
"duration": "three one-hour treatments every day (patient); duration for animals not stated"
},
"population": "Patient with triple negative breast cancer brain metastasis; preclinical models (animals) implanted with brain metastasis PDXs or brain-tropic cell lines",
"sample_size": null,
"outcomes": [
"Tumor growth and metastases in animal models",
"Growth suppression of patient-derived xenografts (PDXs) from brain metastases",
"Clinical regression of brain metastasis in a patient with triple negative breast cancer",
"Mechanistic endpoints: Ca2+ influx via CACNA1H T-type channels; CAMKII/p38 MAPK signaling; suppression of β-catenin/HMGA2 signaling; cancer stem cell inhibition; exosomal miR-1246 downregulation; angiogenesis in brain environment",
"Efficacy in combination with radiation therapy (mentioned)"
],
"main_findings": "27.12 MHz athermal amplitude-modulated RF EMF at breast cancer specific frequencies was associated with decreased growth/metastases in brain-tropic cell line animal models and strong suppression of growth in brain metastasis PDX models. The authors report significant and durable regression of a brain metastasis in one patient, and propose mediation via Ca2+ influx through CACNA1H with downstream signaling changes and reduced angiogenesis-related markers.",
"effect_direction": "benefit",
"limitations": [
"Clinical evidence described for a single patient; broader clinical sample size not provided in abstract",
"Animal study details (numbers, randomization/blinding) not provided in abstract",
"Exposure dosimetry (e.g., SAR) not reported in abstract"
],
"evidence_strength": "very_low",
"confidence": 0.7399999999999999911182158029987476766109466552734375,
"peer_reviewed_likely": "yes",
"keywords": [
"radiofrequency electromagnetic fields",
"amplitude-modulated",
"athermal",
"27.12 MHz",
"breast cancer specific frequencies",
"brain metastasis",
"patient-derived xenograft",
"CACNA1H",
"T-type calcium channel",
"Ca2+ influx",
"CAMKII",
"p38 MAPK",
"β-catenin",
"HMGA2",
"exosomal miR-1246",
"angiogenesis",
"radiation combination"
],
"suggested_hubs": []
}
AI can be wrong. Always verify against the paper.
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