Hyperthermia Cancer Research Results

HPT, Hyperthermia: Click to Expand ⟱

Features:

Mild Hyperthermia (Approximately 39°C to 41°C
Pathways and Effects:
-Heat Shock Protein (HSP) Induction: Mild heat stress triggers the production of HSPs (e.g., HSP70, HSP90) that help cells cope with stress, which can sometimes provide a transient protective effect. However, these proteins can also act as immunomodulators.
-Modulation of the Immune System: Mild hyperthermia can enhance dendritic cell activation and improve antigen presentation, leading to the stimulation of anti-tumor immune responses.
-Vasodilation: Increased blood flow and improved oxygenation can sensitize tumors to radiation therapy and certain chemotherapeutics.

Moderate Hyperthermia (Approximately 41°C to 43°C)
Pathways and Effects:
-Enhanced Cytotoxicity: At temperatures in this range, tumor cells become more vulnerable to radiation and some chemotherapeutic agents. This is partly due to the inhibition of DNA repair pathways.
-Increased Permeability: Moderate heat can increase the permeability of cellular membranes, aiding in drug delivery and the uptake of chemotherapeutic agents.
-Induction of Apoptosis: Elevated temperatures can trigger apoptotic signaling pathways in cancer cells, sometimes in conjunction with other therapies.

High Hyperthermia / Thermal Ablation (Approximately 43°C to 50°C and above)
Pathways and Effects:
-Direct Cytotoxicity: High temperatures can lead to protein denaturation, membrane disruption, and direct cell death.
-Coagulative Necrosis: Sustained high temperatures cause irreversible cell injury leading to necrosis of tumor tissues.
-Vascular Damage: Hyperthermia in this range can damage tumor vasculature, reducing blood supply and indirectly causing tumor cell death.
-Enhanced Immune Response: Although high temperatures can cause immediate cell death, the release of tumor antigens and damage-associated molecular patterns (DAMPs) can stimulate an anti-tumor immune response

Hyperthermia — a physical anticancer treatment modality in which tumor tissue is deliberately heated, usually to approximately 39–43°C for tens of minutes, using electromagnetic energy, ultrasound, infrared heating, heated perfusate, or related techniques. It is formally classified as a thermal therapy rather than a drug and is most commonly abbreviated HT; the Nestronics database uses HPT. Local, superficial, interstitial, and regional hyperthermia are distinct from thermal ablation, where substantially greater thermal doses are intended to directly destroy tissue. Therapeutic hyperthermia is primarily used as an adjunct to radiotherapy or chemotherapy rather than as a stand-alone systemic cancer treatment. Its biological activity depends strongly on temperature, duration, spatial temperature distribution, tumor perfusion, and timing relative to other therapy.

Primary mechanisms (ranked):

Radiosensitization through inhibition of DNA-damage repair, particularly transient suppression of homologous recombination through BRCA2 degradation and impaired RAD51-dependent repair.
Proteotoxic stress and disruption of protein folding, macromolecular complexes, membranes, and cytoskeletal structures as thermal dose increases.
Tumor perfusion and oxygenation modulation; mild hyperthermia can increase blood flow and reduce hypoxia, thereby increasing radiation sensitivity.
Chemosensitization through increased tumor perfusion and drug delivery, membrane permeability, impaired DNA repair, and heat-dependent enhancement of cytotoxic drug activity.
Mitochondrial and cellular stress leading to apoptosis and, at greater thermal doses, irreversible necrotic cell injury.
Heat-shock response with HSF1-driven HSP70/HSP90 induction; this is an important adaptive counter-response that can produce thermotolerance and partially oppose therapeutic cytotoxicity.
Immune modulation through stress-protein signaling, antigen release, DAMP-associated signaling, and altered immune-cell trafficking and antigen presentation.
ROS and oxidative-stress amplification as a secondary, temperature- and model-dependent contributor to mitochondrial injury, apoptosis, and radiosensitization.

Bioavailability / PK relevance: Not applicable in the conventional pharmacokinetic sense because hyperthermia is a locally delivered physical modality rather than a circulating drug. The analogous exposure variable is thermal dose, commonly characterized by achieved temperature, treatment duration, spatial coverage, and metrics such as cumulative equivalent minutes at 43°C. Clinical effectiveness depends on adequate and reasonably homogeneous heating of the target while limiting normal-tissue hot spots. Tumor depth, perfusion, tissue composition, applicator geometry, coupling, thermometry, and treatment planning are therefore major delivery constraints.

In-vitro vs systemic exposure relevance: Hyperthermia is not concentration-driven. In-vitro temperature exposures can be tightly controlled and spatially uniform, whereas clinical tumors commonly exhibit substantial temperature heterogeneity. Mechanistic findings obtained at 41–43°C are clinically relevant when comparable intratumoral thermal doses are actually achieved; experiments at higher temperatures or prolonged exposures increasingly model thermal ablation rather than conventional oncologic hyperthermia.

Clinical evidence status: RCT-supported adjunct treatment in selected cancers, particularly in combination with radiotherapy, re-irradiation, or chemotherapy. Randomized studies demonstrate improved local response or progression-related outcomes in settings including superficial or recurrent breast tumors, locally advanced pelvic tumors, and high-risk soft-tissue sarcoma. Survival benefit is disease- and regimen-dependent and has not been demonstrated uniformly. Hyperthermia remains specialized and is not widely available. FDA-regulated RF/microwave hyperthermia systems have been cleared or approved for defined oncologic indications. Major practical limitations are achieving adequate target thermal dose, avoiding normal-tissue hot spots, specialized equipment and expertise, and integration with radiotherapy or chemotherapy. Local adverse effects include discomfort, pain, burns and blistering; regional perfusion and whole-body techniques have additional systemic risks.

Hyperthermia Cancer-Relevant Mechanisms

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	DNA repair inhibition and radiosensitization	BRCA2 ↓; RAD51-dependent HR ↓; radiation sensitivity ↑	DNA repair may also be heat-sensitive, but normally perfused tissue is generally more thermally protected	R	Radiosensitization ↑	One of the best-defined molecular mechanisms. Approximately 41–43°C can transiently impair homologous recombination, creating a period of increased sensitivity to ionizing radiation and potentially other DNA-damaging therapies.
2	Proteotoxic stress and protein stability	Protein unfolding ↑; aggregation ↑; proteostasis stress ↑	Proteotoxic stress ↑ (dose-dependent)	P, R	Cellular stress and thermal cytotoxicity ↑	Heat directly alters protein conformation and macromolecular complexes. Direct cytotoxicity becomes progressively more important as thermal dose increases.
3	Tumor perfusion and oxygenation	Blood flow ↑; oxygenation ↑; hypoxia ↓ (mild hyperthermia, context-dependent)	Perfusion ↑	P, R	Radiation response ↑; drug delivery may ↑	Often strongest around mild temperatures near 39–42°C. At excessive thermal doses vascular function can instead deteriorate, so the direction is temperature- and tissue-dependent.
4	Chemosensitization	Drug delivery ↑; drug cytotoxicity ↑; DNA repair capacity ↓ (drug-dependent)	Drug exposure or toxicity may ↑ locally	R, G	Chemotherapy efficacy ↑	Synergy is agent-specific. Mechanisms include improved perfusion, altered membrane transport and protein function, and interference with repair of chemotherapy-induced DNA damage.
5	Heat shock response and thermotolerance	HSF1 ↑; HSP70/HSP90 ↑; thermotolerance ↑	HSPs ↑; cytoprotection ↑	R, G	Adaptive resistance ↑	A major counter-regulatory mechanism rather than a purely anticancer effect. Prior heat exposure can reduce sensitivity to subsequent heating, making treatment interval and thermal history important.
6	Mitochondrial injury and intrinsic apoptosis	Mitochondrial dysfunction ↑; membrane potential ↓; cytochrome c release ↑; apoptosis ↑	Mitochondrial injury ↑ at excessive thermal dose	R, G	Programmed cell death ↑	Importance rises with temperature and exposure duration. Tumor susceptibility varies substantially among cell types.
7	Membrane and cytoskeletal disruption	Membrane fluidity and permeability ↑; trafficking disruption ↑; cytoskeletal stress ↑	Similar changes ↑ (dose-dependent)	P, R	Cell stress and drug uptake ↑	Provides one contributor to heat-mediated chemosensitization but is not selectively confined to malignant cells.
8	Immune and DAMP signaling	DAMP release ↑; extracellular HSP signaling ↑; tumor-antigen availability ↑	Immune-cell trafficking and activation ↝ (context-dependent)	G	Antitumor immune visibility ↑	Potentially useful for combination with radiotherapy and immunotherapy, but clinical magnitude depends strongly on thermal regimen, tumor type, immune context, and concurrent treatment.
9	Oxidative and mitochondrial ROS stress	ROS ↑ (secondary, dose-dependent); oxidative damage ↑	ROS ↑ at sufficient thermal stress	P, R	Stress signaling and cell death ↑	Mechanistically relevant in multiple experimental systems but less central and less universal than DNA-repair inhibition, proteotoxicity, and perfusion-mediated radiosensitization.
10	Direct thermal cell death	Apoptosis ↑; necrosis ↑ as thermal dose rises	Collateral thermal injury ↑ at excessive dose	R, G	Tumor cell survival ↓	Conventional hyperthermia emphasizes sensitization and sublethal thermal stress. At substantially greater temperature-time exposures direct coagulative injury dominates and treatment should more appropriately be classified as thermal ablation.
11	Clinical Translation Constraint	Therapeutic effect depends on temperature coverage, duration, tumor perfusion, depth, and combination-treatment timing	Hot spots can cause pain, burns, blistering, or deeper tissue injury	P, R, G	Reproducibility and therapeutic window limitation	No conventional PK applies. Thermal heterogeneity, applicator geometry, thermometry, treatment planning, patient anatomy, tumor perfusion, and specialized equipment are major determinants of clinical efficacy. Evidence supports selected adjunct applications rather than universal use across cancers.

P: 0–30 min R: 30 min–3 hr G: >3 hr

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Scientific Papers found: Click to Expand⟱

333-

AgNPs,

HPT,

Enhancement effect of cytotoxicity response of silver nanoparticles combined with thermotherapy on C6 rat glioma cells

in-vivo,

GBM,

rat

OS↑,

4358-

AgNPs,

HPT,

Rad,

Silver nanocrystals mediated combination therapy of radiation with magnetic hyperthermia on glioma cells

in-vitro,

GBM,

U251

10 nm silver nanoparticles (AgNPs) on human glioma U251 c

RadioS↑, AgNPs showed both radio and thermo sensitivity on U251 cells from the surviving fraction curve.
eff↑, both X-rays and heat could enhance the content of cells uptake of AgNPs.
TumCD↑, potential application in enhancing effect of RT with MHT combination therapy induced killing of cancer cells.

7623-

HPT,

Rad,

Enhancing radiosensitisation of BRCA2-proficient and BRCA2-deficient cell lines with hyperthermia and PARP1-i

Review,

Var,

BRCA2↓, Recently, BRCA2 was shown to be down-regulated by hyperthermia (HT) temporarily, and this consequently inactivated HR for several hours.
RadioS↑, BRCA2-proficient and deficient cells are radiosensitised by HT, indicating that HT does not exclusively act by inhibition of HR.
eff↑, This combination therapy would be effective for all patients with PARP1-i regardless of their BRCA status.

7577-

HPT,

Rad,

Randomized trial of hyperthermia and radiation for superficial tumors

Trial,

Var,

 One hundred twenty-two patients were enrolled; 109 (89%) were deemed heatable and were randomly assigned

RadioS↑, Randomized clinical trials have demonstrated hyperthermia (HT) enhances radiation response
eff↑, The complete response rate was 66.1% in the HT arm and 42.3% in the no-HT arm
Dose↝, thermal dose of

7597-

HPT,

Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group

Trial,

Var,

. 358 patients

ORR↑, Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia
OS↑, 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group

7598-

HPT,

Rad,

Chemo,

The role of capacitive hyperthermia as an adjunct treatment in oncology: a systematic review of randomized phase III trials

Review,

Var,

nine randomized phase III trials were included in the study.

OS↑, It has been demonstrated that the combination of cHT with either RT or CT may improve TR and LC and, in certain cases, OS when compared with RT with or without CT alone
TR↑,
LC↑,
*toxicity?, The occurrence of significant side effects is rare.

7599-

HPT,

Rad,

Recent development on hyperthermia: An effective cotreatment improving radiotherapy outcome

Review,

Var,

NA↑, As an adjunct to radiotherapy and chemotherapy, hyperthermia enhances the therapeutic efficacy against both primary and recurrent tumors.
RadioS↑, The present review explores the mechanisms underlying the synergy between radiotherapy and hyperthermia, while reviewing the outcomes of relevant clinical trials.
DNArepair↓, Key mechanisms of action include inhibition of DNA repair, reduction of hypoxic tumor cell populations, enhancement of drug uptake and improved perfusion and oxygenation.
Hypoxia↓,
EPR↑,
LC↑, Its application has improved both local control and overall survival (OS),
OS↑,
*toxicity↓, Randomized clinical trials (4–6) have demonstrated that combined therapy effectively prolongs disease-free survival and ensures local tumor control without added toxicity.
Dose↝, fever-range temperatures (39–40°C), moderate heating to induce cellular stress (41–43°C) and high-intensity thermal ablation >43°C for cell destruction.
BloodF↑, Hyperthermia is particularly toxic to cells in acidic environments (29), and increased blood flow helps clear acidic metabolites, restore normal extracellular pH
pH↝,
Imm↑, Under heat stress, tumor cells release heat shock protein 70 (HSP70), triggering antitumor immune responses
HSP70/HSPA5↑,

7618-

HPT,

ESHO 2-85. Hyperthermia as an adjuvant to radiation therapy in the treatment of advanced neck nodes: A randomized multicenter study by the European Society for Hyperthermic Oncology

ORR↑, complete response rate was 53% in the RT versus 80% in the RT+HT group, and 3-year persistent local control rate was 32% for RT alone versus 53% for RT+HT; HR: 0.48 [0.23–0.98].
NA↑, The ESHO 2–85 study demonstrated that addition of a weekly HT treatment to RT of advanced neck nodes significantly enhanced the persistent tumor control.
NA↑, HT was associated with moderate to severe pain and discomfort in 38% of the treatments.
BioAv↝, The clinical application of heat was (and still is) hampered by the difficulties to provide a homogeneous heating to a given target.
Dose↝, Each heat session should aim for a minimal tumor temperature 60 min at 43.0°C or equivalen
Dose↝, HT was applied with electromagnetic heating.

7619-

HPT,

The role of hyperthermia in the treatment of tumor

Imm↑, HT also serves as an immune adjuvant strategy in radiotherapy, chemotherapy, and immunotherapy, enhancing the effectiveness of radiotherapy, increasing the uptake of chemotherapy drug
RadioS↑,
ChemoSen↑,
EPR↑,

7620-

HPT,

Hyperthermia and radiotherapy: physiological basis for a synergistic effect

Review,

Var,

RadioS↑, mild hyperthermia (HT) represents an old, but recently revived opportunity to increase the efficacy of radiotherapy (RT) without increasing side effects, thereby widening the therapeutic window.
DNArepair↓, associated to DNA damage and repair, hypoxia, stemness and immunostimulation.
Hypoxia↓,
CSCs↓, Some evidences suggests that HT may be able to radiosensitize CSCs, as well as quiescent tumor cells,
Imm↑, Heat-induced activation of the immune system is mediated by heat shock proteins (HSPs); they increase antigen presentation and maturation of dendritic cells,
pH↝, regains a normal oxygen partial pressure (pO2), a normal concentration of nutrients and a normal pH, which reverse the established radioresistance
HSPs↑,
ROS↑, Hyperthermia potentializes the effects of irradiation by reducing DNA damage repair, increasing oxygen levels by vessel dilation, increasing ROS,
eff↑, An increasing number of preclinical and clinical studies are focusing on heating tumors with nanoparticles

7621-

HPT,

Rad,

Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study

Trial,

Pca,

Trial,

BC,

Pain↓, WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.
Dose↝, WBH application time was 3-4 h in three fractions with at least 48-h intervals.
CR↑, Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment

7622-

HPT,

A Review of the Current Clinical Evidence for Loco-Regional Moderate Hyperthermia in the Adjunct Management of Cancers

Review,

Var,

LC↑, moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities.
OS↑,
QoL↑,
toxicity↓,
Dose↝, Various heating methods include direct (e.g., intracavitary and whole-body waterbed), infrared, perfusional (e.g., isolated limb perfusion, intravesical and intraperitoneal), nanoparticles, ultrasound and regional radiofrequency (RF) radiation
Dose↝, Moderate HT is usually described at a range of 39–44 °C a
ROS↑, Figure 1
DNArepair↓,
EPR↑,
DNAdam↑,
HSP70/HSPA5↑,
BloodF↑,
Hypoxia↓,

7575-

HPT,

Rad,

Chemo,

immuno,

From Localized Mild Hyperthermia to Improved Tumor Oxygenation: Physiological Mechanisms Critically Involved in Oncologic Thermo-Radio-Immunotherapy

RadioS↑, Mild hyperthermia (mHT, 39–42 °C) is a potent modality when combined with existing radio-, chemo-, or immunotherapy, leading to enhanced microcirculatory blood flow and improved tumor oxygenation
ChemoSen↑, Hyperthermia enhances cytotoxicity of anticancer drugs:
Imm↑,
BloodF↑,
Hypoxia↓, HT-induced improvements of tumor oxygenation status (“reversal of tumor hypoxia”) a
Dose↝, Mild hyperthermia (mHT, 39–42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy.
DNArepair↓, Hyperthermia inhibits DNA repair enzymes: In the upper range of mHT (41–43 °C), several DNA damage repair enzymes responsible for the repair
e-pH↓, Tissue exposure to mHT triggers a series of events that aggravate tumor tissue acidosis (pH↓), finally reaching extracellular pH values of ≈ 6.20:

7624-

HPT,

Chemo,

A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer

Trial,

Cerv,

, 101 patients were treated.

OS↑, Although not statistically significant, the 5-year OS, DFS and LRFS in the CRT + HT group (77.8%, 70.8% and 80.1%, respectively) were better than those in the CRT group (64.8%, 60.6% and 71.0%, respectively). C
CR↑, CR was significantly more likely to be achieved in patients in the CRT + HT group than in the CRT group (88% vs. 77.6%; adjusted odds ratio, 3.993; 95% confidence interval, 1.018-15.67; p = .047).
*toxicity↓, CRT + HT was well tolerated and caused no additional acute or long-term toxicity compared with CRT alone.

7626-

HPT,

Rad,

Dynamics of chromosomal aberrations, induction of apoptosis, BRCA2 degradation and sensitization to radiation by hyperthermia

in-vitro,

NA,

BRCA2↓, Hyperthermia can transiently degrade BRCA2 and thereby inhibit the homologous recombination pathway.
selectivity↑, Cell survival experiments demonstrated that exposure to hyperthermia radiosensitized the RKO cells, but not the SW‑1573 cells.
RadioS↑, This radiosensitization was at least partly due to the induction of apoptosis, which was only observed in the RKO cells and which may have been induced by BRCA2 degradation
eff↝, genotoxic effect of hyperthermia shortly after combined epxosure (to hyperthermia and radiation) is not observed at 24 h after treatment.

7627-

HPT,

Rad,

Local control rate after the combination of re-irradiation and hyperthermia for irresectable recurrent breast cancer: Results in 248 patients

CR↑, CR rate was 70%. At 1, 3, and 5 years LC was 53%, 40% and 39%, and OS was 66%, 32%, and 18%, respectively.
OS↑, OS after 10 years was 10%.
*toxicity↝, Thermal burns developed in 23% patients, healing with conservative measures. T
RadioS↑, The combination of re-RT and HT results in a high rate of long-term LC with acceptable late toxicity, and many patients remained locally controlled for the rest of their survival period.

7649-

HPT,

Rad,

A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy

in-vivo,

Laryn,

FaDu

Mice

Dose↝, Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h
BloodF↑, Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models
Hypoxia↓, Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment.
RadioS?, Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice.

7650-

HPT,

Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer

Trial,

BC,

127 patients received HT and RT to 167 sites.

OS↑, At a median follow-up of 13 months (mean 30±38), improved overall survival was significantly associated with increasing RT dose (p<0.0001), median TED 42.5°C≥200 minutes (p=0.003), and local control (p=0.0002).
LC↑,

7651-

HPT,

Rad,

Hyperthermia inhibits homologous recombination repair and sensitizes cells to ionizing radiation in a time- and temperature-dependent manner

in-vitro,

Var,

RadioS↑, Hyperthermia has long been known as a radio-sensitizing agent that displays anti-tumor effects, and has been developed as a therapeutic application.
DNArepair↓, The mechanisms of hyperthermia-induced radio-sensitization are highly associated with inhibition of DNA repair.
Dose↑, Significant differences in cellular toxicity attributable to hyperthermia at and above 42.5°C were observed.

7675-

HPT,

Quality assurance protocol for superficial and deep hyperthermia systems established by the Hellenic Association of Medical Physicists (HAMP) in cooperation with the Hellenic Society of Oncologic Hyperthemia (HSOH): A study based on European Society for Hyperthermic Oncology (ESHO) quality assurance guidelines

Review,

Var,

NA↝, The proposed protocol, applied by medical physicists in Greece, will ensure an efficient treatment with safety and minimum adverse effects.

886-

HPT,

Impact of hyper- and hypothermia on cellular and whole-body physiology

Analysis,

NA,

MMP↓,
OXPHOS↓, impaired oxidative phosphorylation
ATP↓,
ROS↑, increase reactive oxygen species (ROS) production within mitochondria,
Apoptosis↑,
Cyt‑c↑, releasing cytochrome c into the cytoplasm

7574-

HPT,

Oxy,

Improvement of tumor oxygenation by mild hyperthermia

Hypoxia↓, There is now abundant evidence that oxygenation in rodent, canine and human tumors is improved during and for up to 1-2 days after heating at mild temperatures.
OCR↓, An increase in tumor blood perfusion along with a decline in the oxygen consumption rate appears to account for the improvement of tumor oxygenation by mild hyperthermia
RadioS↑, However, mild hyperthermia is far more effective than carbogen breathing in increasing the radiation response of experimental tumors,
eff↑, The combination of mild hyperthermia with carbogen or nicotinamide is highly effective in reducing the hypoxic cell fraction in tumors and increasing the radiation response of experimental tumors.
Dose↝, However, it is relatively easy to raise the temperature of human tumors into the range of 39-42 degrees C, which is a temperature that can improve tumor oxygenation for up to 1-2 days.

7573-

HPT,

Rad,

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

vitro+vivo,

NA,

RadioS↑, Hyperthermia (40-44 °C) effectively sensitises tumours to radiotherapy by locally altering tumour biology
BRCA2↓, We found decreased BRCA2-levels after hyperthermia in all established cell lines and in 91% of all tumours treated ex vivo.

7572-

HPT,

Rad,

The effect of thermal dose on hyperthermia-mediated inhibition of DNA repair through homologous recombination

in-vitro,

Cerv,

HeLa

in-vitro,

Laryn,

FaDu

RadioS↑, Hyperthermia has a number of biological effects that sensitize tumors to radiotherapy in the range between 40-44 °C.
TumCD↑, For treatment temperatures above 41 °C, we found a decrease in cell survival, an increase in sensitization towards irradiation, a decrease of BRCA2 protein levels, and altered RAD51 focus formation.
BRCA2↓,
Dose↝, This study demonstrates that optimal inhibition of HR is achieved by subjecting cells to hyperthermia at 41-43 °C for 30 to 60 minutes.
BloodF↑, The second explanation is that hyperthermia has multiple biological effects, including increased blood flow [33], increased oxidation [34], and activation of the immune system
ROS↑,
Imm↑,

7571-

HPT,

Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition

vitro+vivo,

Var,

BRCA2↓, mild hyperthermia (41–42.5 °C) induces degradation of BRCA2 and inhibits HR
eff↑, We demonstrate that hyperthermia can be used to sensitize innately HR-proficient tumor cells to PARP-1 inhibitors and that this effect can be enhanced by heat shock protein inhibition.
RadioS↑, HeLa cells, in which the important HR factors XRCC3 or BRCA2 were down-regulated using siRNA, were refractory to further temperature-mediated radiosensitization

5054-

HPT,

Induction of Oxidative Stress by Hyperthermia and Enhancement of Hyperthermia-Induced Apoptosis by Oxidative Stress Modification

Review,

Var,

eff↓, However, clinical results by HT alone have not always been satisfactory
ROS↑, One of these HT-induced alterations, oxidative stress, has been attributed to the increased production of reactive oxygen spaces (ROS), and is known to play an important role as an intracellular mediator of HT-induced cell death, including apoptosis.
Apoptosis↑,

5053-

HPT,

Rad,

Chemo,

Association of elevated reactive oxygen species and hyperthermia induced radiosensitivity in cancer stem-like cells

in-vitro,

Var,

CSCs↓, SCs were found to be more susceptible to radiation when combined with HT treatment
TumCP↓, Treated cells showed significantly reduced self-renewal, cell survival and proliferation in vitro, as well as significant reduced tumor formation in vivo.
ROS↑, Further study demonstrated that the radiosensitization effect was associated with increased intracellular reactive oxygen species (ROS) level in CSCs, confirmed by modifying redox status in CSCs bidirectionally.
RadioS↑, new strategy for improving CSCs radiosensitivity

5052-

HPT,

Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells

in-vitro,

OS,

U2OS

Apoptosis↑, Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells.
ROS↑, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells.
Casp3↑,
mtDam↑, Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax.
Cyt‑c↑,
Bcl-2↓,
Bcl-xL↓,
Bak↑,
BAX↓,
ER Stress↑, Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity.
Ca+2↝,
cal2↑,

5051-

HPT,

doxoR,

Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells

in-vitro,

Melanoma,

A375

tumCV↓, Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration.
TumCCA↑, Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels.
ROS↑,
eff↑, These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.

5050-

HPT,

Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review

Review,

Nor,

*ROS↑, Heat stress was suggested to be an environmental factor responsible for stimulating ROS production because of similarities in responses observed following heat stress compared with that occurring following exposure to oxidative stress.
*SOD1↓, Heat stress was also shown to decrease superoxide dismutase 1 (SOD-1) mRNA levels, cytoplasmic SOD protein and enzyme activity, leading to the increase of ROS generation
*GSH↓, Furthermore, several studies demonstrated that heat stress results in a dramatic decrease in glutathione (GSH) levels.
other↑, Nowadays, a variety of diseases and degenerative processes such as cancer, Alzheimer’s and autoimmune diseases are mediated by oxidative stress.
HIF-1↑, heat stress activates hypoxia-inducible factor 1 (HIF-1) through ERK-NADPH oxidase-mediated ROS production, and this enhances tumour oxygenation by up-regulating HIF-1 target gene
ROS↑,

5049-

HPT,

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

vitro+vivo,

PC,

Panc02

vitro+vivo,

PC,

Bxpc-3

tumCV↓, The thermal effects were confirmed by the following observations: 1) decreased number of vital cells,
proCasp↑, 2) altered expression of pro-caspases, and
ROS↑, 3) production of reactive oxygen species, and
Ki-67↓, 4) altered mRNA expression of Ki-67, TOP2A, and TPX2.
TOP2↓, mRNA expression of the proliferation markers Ki-67, TOP2A, and TPX2 revealed a marked reduction in their expression after PANC-1 cells were treated with MH
TumVol↓, The MH treatment of tumor xenografts significantly (P≤0.05) reduced tumor volumes.

2257-

MF,

HPT,

HSP70 Inhibition Synergistically Enhances the Effects of Magnetic Fluid Hyperthermia in Ovarian Cancer

in-vitro,

Ovarian,

eff↑, HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer.
eff↑, A significantly reduction in tumor growth rate was observed with combination therapy

2256-

MF,

HPT,

Effects of exposure to repetitive pulsed magnetic stimulation on cell proliferation and expression of heat shock protein 70 in normal and malignant cells

in-vitro,

BC,

MCF7

34mT, 50Hz 2-s bursts and 1-s rests.

in-vitro,

Cerv,

HeLa

in-vitro,

Nor,

HBL-100

HSP70/HSPA5↑, HSP70 expression was increased by RPMS exposure under thermal stress at 40 degrees C and 42 degrees C in HBL-100 and HeLa.
HSP70/HSPA5∅, HSP70 was not affected by RPMS at 37°C (Fig. 5A).

2252-

MF,

HPT,

Cellular Response to ELF-MF and Heat: Evidence for a Common Involvement of Heat Shock Proteins?

Review,

NA,

HSPs∅, In some studies, no HSP-related effects were detected after ELF-MF exposure ranging from a few μT to mT and from minutes to 24 h, using different cell types such as astroglial cells (30), HL-60, H9c2, and Girardi heart cells (31, 32), and human kerat
*HSPs↑, exposure has also caused changes in HSP levels in a number of primary or non-transformed (“primary like”) cell lines.
eff↝, The hypothesis that non-stressed cells or organisms are quite responsive to HSP induction after ELF-MF exposure is strengthened by some in vivo studies in invertebrates
*eff↑, ELF-MF Exposure Potentiates the Effects of Heat on HSP Induction
eff↑, Interestingly, when HeLa and HL-60 cancer cells were subjected to comparable magnetic flux densities (10–140 µT), exposure durations (20–30 min) and concurrently heat stressed at 43°C, a stronger HSP70 expression was attained in coexposed cells
eff↓, An interesting finding is that MF exposure provides protection against heat-induced effects such as apoptosis, cell cycle disturbances, or proliferation inhibition in both cell models and in organisms

1674-

PBG,

SDT,

HPT,

Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells

in-vitro,

PC,

PANC1

in-vitro,

Nor,

H6c7

tumCV↓, cell viability of a human cancer cell line PANC-1 decreased to a level 80% less than the control
ROS↑, triple treatment showed a significant accumulation of the intracellular ROS (up to a 2.1-fold increase)
eff↑, combination of TC-HT and US also promotes the anticancer effect of the heat-sensitive chemotherapy drug cisplatin on PANC-1 cells
Dose∅, moderate propolis concentration 0.3%, 10-cycles TC-HT and 2.25 MHz US with intensity 0.3 W/cm2 and duration 30 minutes were chosen to avoid the thermotoxicity on PANC-1 cells
selectivity↑, Moreover, normal cells such as the human skin cells Detroit 551 (Figure 1D) and human pancreatic duct cells H6c7 (Figure 1E) were not significantly affected by the triple treatment as well as all the other treatments.
MMP↓, ratio of the cells exhibiting MMP loss was significantly promoted to 23.3% after the double treatment of propolis + TC-HT, and it was further elevated significantly to 34.7% by employing the triple treatment.
mtDam↑, hence caused more mitochondrial dysfunction
cl‑PARP↑, PARP cleavage was further promoted significantly to a 6.2-fold increase by US in the triple treatment
p‑ERK↓, the p-ERK level was suppressed by propolis + TC-HT treatment (0.30-fold decrease), and was further down-regulated when US was introduced in the triple treatment (0.15-fold decrease)
p‑JNK↑, p-JNK and p-p38 levels both exhibited a reverse performance, which were promoted the most in the triple treatment (8.7-fold and 9.2-fold increase, respectively)
p‑p38↑,
eff↓, inhibitory effect of the triple treatment was restored by NAC
ChemoSen↑, cisplatin + TC-HT treatment significantly elevated PARP cleavage to a 3.20-fold increase. This elevation was further increased with the help of US (5.82-fold increase).

97-

QC,

HPT,

Effects of the flavonoid drug Quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo

in-vitro,

Pca,

PC3

 0-400 uM; 150mg/kg/day

HSP72↑, Quercetin in prostate cancer treatment is that it antagonizes HSP72 production and, thus, sensi- tizes cells to hyperthermia-induce d apoptosis
TumCG↓, Quercetin dose-dependently suppressed PC-3 tumour growth in vitro and in vivo.
eff↑, suggest the use of Quercetin as a hyperthermia sensitizer in the treatment of prostate carcinoma
ChemoSen↑, Quercetin can act as a sensitizer to hyperthermia (® gures 1± 5), chemotherapeutic agents and ionizing radiation4,20
RadioS↑,

94-

QC,

HPT,

Effects of quercetin on the heat-induced cytotoxicity of prostate cancer cells

in-vitro,

Pca,

LNCaP

 12.5, 25, 50, 100 umol/L

in-vitro,

Pca,

PC3

in-vitro,

Pca,

JCA-1

HSP70/HSPA5↓, Quercetin inhibited an increase of hsp70 expression after heat treatment and increased the number of subG1 cells with lower levels of hsp70 in JCA-1 and LNcap cells.
TumCCA↑,
TumCG↓, Quercetin inhibited the growth of JCA-1 and LNcap cells at concentrations over 12.5 mmol/L.
eff↑, the presence of quercetin during heating enhances the growth-inhibitory effect of heat by inducing apoptosis in the JCA-1 and LNcap cells.

7576-

Rad,

HPT,

Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group

Trial,

Nor,

 306 patients randomized.

RadioS↑, The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer.

Showing Research Papers: 1 to 38 of 38

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 38

Pathway results for Effect on Cancer / Diseased Cells:

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 5,

Cellular Microenvironment(tgid=17) ⓘ

pH↝, 2, e-pH↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1, ChemoSen↑, 4, Dose↑, 1, Dose↝, 11, Dose∅, 1, eff↓, 3, eff↑, 13, eff↝, 2, RadioS?, 1, RadioS↑, 17, selectivity↑, 2,

Clinical Biomarkers(tgid=22) ⓘ

BloodF↑, 5, Ki-67↓, 1,

Functional Outcomes(tgid=23) ⓘ

OS↑, 8, Pain↓, 1, QoL↑, 1, toxicity↓, 1, TumVol↓, 1,
Total Targets: 69

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

GSH↓, 1, ROS↑, 1, SOD1↓, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

HSPs↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,

Functional Outcomes(tgid=23) ⓘ

toxicity?, 1, toxicity↓, 2, toxicity↝, 1,
Total Targets: 8

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:98  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Hyperthermia Cancer Research Results

Hyperthermia Cancer-Relevant Mechanisms

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Functional Outcomes(tgid=23) ⓘ

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