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1.
Med Oncol ; 39(12): 181, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071292

RESUMO

Since the first definition by Hellman and Weichselbaum in 1995, the concept of OligoMetastatic Disease (OMD) is a growing oncology field. It was hypothesized that OMD is a clinical temporal window between localized primary tumor and widespread metastases deserving of potentially curative treatment. In real-world clinical practice, OMD is a "spectrum of disease" that includes a highly heterogeneous population of patients with different prognosis. Metastasis directed therapy with local ablative treatment have proved to be a valid alternative to surgical approach. Stereotactic body radiation therapy demonstrated high local control rate and increased survival outcomes in this setting with a low rate of toxicity. However, there is a lack of consensus regarding many clinical, therapeutic, and prognostic aspects of this disease entity. In this review, we try to summarize the major critical features that could drive radiation oncologists toward a better selection of patients, treatments, and study endpoints. With the help of a set of practical questions, we aim to integrate the literature discussion.


Assuntos
Neoplasias , Radiocirurgia , Consenso , Humanos , Neoplasias/patologia , Neoplasias/radioterapia , Prognóstico , Radio-Oncologistas
2.
Methods Cell Biol ; 172: 145-161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36064221

RESUMO

It is now clear that radiation therapy (RT) can be delivered in doses and according to fractionation schedules that actively elicit immunostimulatory effects. While such effects are often sufficient to drive potent anticancer immunity culminating with systemic disease eradication, the immunostimulatory activity of RT stands out as a promising combinatorial partner for bona fide immunotherapeutics including immune checkpoint inhibitors (ICIs). Accumulating preclinical and clinical evidence indicates that the secretion of type I interferon (IFN) by irradiated cancer cells is a sine qua non for RT to initiate ICI-actionable tumor-targeting immune responses. Here, we detail a simple protocol to quantitatively assess type I IFN responses in irradiated mouse hormone receptor (HR)+ TS/A cells by RT-PCR. With minimal variations, the same technique can be straightforwardly adapted to quantify type I IFN-associated transcriptional responses in a variety of human and mouse cancer cells maintained in vitro.


Assuntos
Neoplasias , Animais , Humanos , Camundongos , Neoplasias/genética , Neoplasias/radioterapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Methods Cell Biol ; 172: 163-178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36064222

RESUMO

Cancer cell-intrinsic type I interferon (IFN-I) activation is required to initiate early innate immune responses and the subsequent radiation-induced anti-tumor immunity. Investigating the secretion of IFN-I cytokines in response to radiation therapy (RT) is therefore a critical readout for selecting the best immunogenic radiation dose-fractionation regimen. In this chapter, we present different ELISA-based quantification techniques that can be utilized to assess the secretion of tumor-derived IFN-I cytokines, namely IFN-α and IFN-ß.


Assuntos
Interferon Tipo I , Neoplasias , Citocinas , Ensaio de Imunoadsorção Enzimática , Imunidade Inata , Interferon Tipo I/farmacologia , Interferon-alfa , Neoplasias/radioterapia
4.
Methods Cell Biol ; 172: 179-189, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36064224

RESUMO

The rapid proliferation of cancer cells and the aberrant vasculature present in most solid tumors frequently result in the lack of oxygen generating a hypoxic tumor microenvironment. Low levels of oxygen not only affect the tumor cell biology and tumorigenesis, but also the other components of the tumor microenvironment such as the tumor stroma and the immune infiltrate, promoting a more suppressive environment. In addition, tumor hypoxia has been associated with reduced sensitivity to chemotherapy (CH) and radiotherapy (RT), leading to poor outcomes in cancer patients. Therefore, the evaluation of tumor oxygen status has become clinically relevant. Tumor hypoxia can be assessed by different methods that include the analysis of the oxygen concentration or the expression of endogenous markers directly related to hypoxia. In this paper, we focus on the use of the hypoxia-specific marker pimonidazole as a straightforward way to measure tumor hypoxia following radiotherapy in a preclinical melanoma model.


Assuntos
Hipóxia , Neoplasias , Biomarcadores/metabolismo , Hipóxia Celular , Humanos , Hipóxia/metabolismo , Neoplasias/radioterapia , Nitroimidazóis , Oxigênio/metabolismo , Coloração e Rotulagem , Microambiente Tumoral
5.
Gan To Kagaku Ryoho ; 49(8): 809-812, 2022 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-36046961

RESUMO

Radiotheranostics is characterized by labeling high quality tumor-seeking compounds with imaging radionuclides for imaging and labeling with therapeutic radionuclides for therapeutic use. Although the nuclear medicine approach of fusing imaging and therapy is no doubt effective, the point is to recognize that it is not always necessary to carry out both imaging and therapy in a series, and how it is effective to carry out imaging and therapy respectively is the point. It may depend largely on the disease that is dealt with. In the therapy, it is of great concern to make optimum use of α emitters in addition to the conventional ß emitters. In the future, theranostics technology and its application to personalized medicine will bring great benefits.


Assuntos
Neoplasias , Radioisótopos , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Medicina de Precisão , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico
6.
JBI Evid Synth ; 20(9): 2378-2386, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36081353

RESUMO

OBJECTIVE: The objective of this review is to evaluate the efficacy and adverse effects of histone deacetylase inhibitors (HDACi) in combination with radiotherapy for the treatment of solid organ malignancies. INTRODUCTION: Histone deacetylase inhibitors are a diverse class of drugs that have shown promise as novel anti-cancer therapeutics via epigenetic modification and radiosensitization of neoplastic cells. The aim of HDACi in combination with radiotherapy is to reduce radiation dosage requirements, improve radiotherapy efficacy, and reduce treatment side effects. INCLUSION CRITERIA: This review will consider studies utilizing HDACi in conjunction with radiotherapy in adult patients with solid organ malignancy. Sources to be included in this review include experimental and quasi-experimental study designs, analytical studies, and descriptive observational studies. METHODS: A systematic review of effectiveness will be conducted in accordance with JBI methodology. A detailed search will be conducted via MEDLINE (Ovid), Embase (Ovid), and Scopus. A search of the Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and ClinicalTrials.gov will also be performed for relevant trials. Inclusion and exclusion criteria will be utilized to select studies, and papers selected for retrieval will be assessed for methodological validity using the JBI critical appraisal instruments. Evidence will be extracted from eligible studies and summarized using quantitative methods, where possible, including meta-analysis and assessment of heterogeneity. Where statistical pooling is not possible, the findings will be presented in diagrammatic or tabular form accompanied by a narrative summary. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021293005.


Assuntos
Inibidores de Histona Desacetilases , Neoplasias , Adulto , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Metanálise como Assunto , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Estudos Observacionais como Assunto , Revisões Sistemáticas como Assunto
7.
Molecules ; 27(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36014472

RESUMO

Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been intensified on the development of radionuclides and their application in radiopharmaceuticals (RPS) which will certainly influence and expand therapeutic approaches in the future treatment of patients. Alpha or beta particles and Auger electrons are used for therapy purposes, and each has advantages and disadvantages. The radionuclides labeled drug delivery system will deliver the particles to the specific targeting cell. Different radioligands can be chosen to uniquely target molecular receptors or intracellular components, making them suitable for personal patient-tailored therapy in modern cancer therapy management. Advances in nanotechnology have enabled nanoparticle drug delivery systems that can allow for specific multivalent attachment of targeted molecules of antibodies, peptides, or ligands to the surface of nanoparticles for therapy and imaging purposes. This review presents fundamental radionuclide properties with particular reference to tumor biology and receptor characteristic of radiopharmaceutical targeted therapy development.


Assuntos
Neoplasias , Compostos Radiofarmacêuticos , Partículas beta , Diagnóstico por Imagem , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico
8.
Sci Rep ; 12(1): 13995, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978040

RESUMO

The dominant consequence of irradiating biological systems is cellular damage, yet microvascular damage begins to assume an increasingly important role as the radiation dose levels increase. This is currently becoming more relevant in radiation medicine with its pivot towards higher-dose-per-fraction/fewer fractions treatment paradigm (e.g., stereotactic body radiotherapy (SBRT)). We have thus developed a 3D preclinical imaging platform based on speckle-variance optical coherence tomography (svOCT) for longitudinal monitoring of tumour microvascular radiation responses in vivo. Here we present an artificial intelligence (AI) approach to analyze the resultant microvascular data. In this initial study, we show that AI can successfully classify SBRT-relevant clinical radiation dose levels at multiple timepoints (t = 2-4 weeks) following irradiation (10 Gy and 30 Gy cohorts) based on induced changes in the detected microvascular networks. Practicality of the obtained results, challenges associated with modest number of animals, their successful mitigation via augmented data approaches, and advantages of using 3D deep learning methodologies, are discussed. Extension of this encouraging initial study to longitudinal AI-based time-series analysis for treatment outcome predictions at finer dose level gradations is envisioned.


Assuntos
Neoplasias , Radiocirurgia , Animais , Inteligência Artificial , Microvasos/diagnóstico por imagem , Microvasos/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Neoplasias/radioterapia , Radiocirurgia/métodos , Dosagem Radioterapêutica , Tomografia de Coerência Óptica/métodos
9.
Cell Death Dis ; 13(8): 709, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974014

RESUMO

Paraspeckles are mammal-specific membraneless nuclear bodies that participate in various biological processes. NONO, a central paraspeckle component, has been shown to play pivotal roles in DNA double-strand breaks (DSB) repair, whereas its underlying mechanism needs to be further disclosed. Here, using co-immunoprecipitation and mass spectrum, we identified ribosomal protein P0 (RPLP0) as a DSB-induced NONO-binding protein; RPLP0 binds to the RRM1 and RRM2 domains of NONO. Similar to NONO, RPLP0 enhances non-homologous end joining-mediated DSB repair, which was ascribed to a ribosome-independent manner. Interestingly, paraspeckles were induced as early as 15 min after irradiation; it further recruited nuclear RPLP0 to enhance its interaction with NONO. Radiation-induced NONO/RPLP0 complex subsequently anchored at the damaged DNA and increased the autophosphorylation of DNA-PK at Thr2609, thereby enhancing DSB repair. Consistently, in vivo and in vitro experiments showed that depletion of NONO sensitizes tumor cells to radiation. For patients with locally advanced rectal cancer, NONO expression was remarkably increased in tumor tissues and correlated with a poor response to radiochemotherapy. Our findings suggest a pivotal role of radiation-induced paraspeckles in DNA repair and tumor radioresistance, and provide a new insight into the ribosome-independent function of ribosomal proteins.


Assuntos
Reparo do DNA , Neoplasias , Paraspeckles , Tolerância a Radiação , Proteínas Ribossômicas , Dano ao DNA , Reparo do DNA por Junção de Extremidades , Proteínas de Ligação a DNA/genética , Humanos , Neoplasias/genética , Neoplasias/radioterapia , Paraspeckles/genética , Proteínas de Ligação a RNA/genética , Tolerância a Radiação/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
10.
Eur J Cancer ; 173: 146-166, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35932626

RESUMO

AIM: To provide practice guidelines about fertility preservation (FP) in oncology. METHODS: We selected 400 articles after a PubMed review of the literature (1987-2019). RECOMMENDATIONS: Any child, adolescent and adult of reproductive age should be informed about the risk of treatment gonadotoxicity. In women, systematically proposed FP counselling between 15 and 38 years of age in case of treatment including bifunctional alkylating agents, above 6 g/m2 cyclophosphamide equivalent dose (CED), and for radiation doses on the ovaries ≥3 Gy. For postmenarchal patients, oocyte cryopreservation after ovarian stimulation is the first-line FP technique. Ovarian tissue cryopreservation should be discussed as a first-line approach in case of treatment with a high gonadotoxic risk, when chemotherapy has already started and in urgent cases. Ovarian transposition is to be discussed prior to pelvic radiotherapy involving a high risk of premature ovarian failure. For prepubertal girls, ovarian tissue cryopreservation should be proposed in the case of treatment with a high gonadotoxic risk. In pubertal males, sperm cryopreservation must be systematically offered to any male who is to undergo cancer treatment, regardless of toxicity. Testicular tissue cryopreservation must be proposed in males unable to cryopreserve sperm who are to undergo a treatment with intermediate or severe risk of gonadotoxicity. In prepubertal boys, testicular tissue preservation is: - recommended for chemotherapy with a CED ≥7500 mg/m2 or radiotherapy ≥3 Gy on both testicles. - proposed for chemotherapy with a CED ≥5.000 mg/m2 or radiotherapy ≥2 Gy. If several possible strategies, the ultimate choice is made by the patient.


Assuntos
Preservação da Fertilidade , Neoplasias , Criopreservação/métodos , Feminino , Preservação da Fertilidade/métodos , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Ovário , Sêmen
11.
Int J Mol Sci ; 23(15)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35955867

RESUMO

Radiation (RT) remains the most frequently used treatment against cancer. The main limitation of RT is its lack of specificity for cancer tissues and the limited maximum radiation dose that can be safely delivered without damaging the surrounding healthy tissues. A step forward in the development of better RT is achieved by coupling it with other treatments, such as photodynamic therapy (PDT). PDT is an anti-cancer therapy that relies on the light activation of non-toxic molecules-called photosensitizers-to generate ROS such as singlet oxygen. By conjugating photosensitizers to dense nanoscintillators in hybrid architectures, the PDT could be activated during RT, leading to cell death through an additional pathway with respect to the one activated by RT alone. Therefore, combining RT and PDT can lead to a synergistic enhancement of the overall efficacy of RT. However, the involvement of hybrids in combination with ionizing radiation is not trivial: the comprehension of the relationship among RT, scintillation emission of the nanoscintillator, and therapeutic effects of the locally excited photosensitizers is desirable to optimize the design of the hybrid nanoparticles for improved effects in radio-oncology. Here, we discuss the working principles of the PDT-activated RT methods, pointing out the guidelines for the development of effective coadjutants to be tested in clinics.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete
12.
BMC Palliat Care ; 21(1): 143, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948925

RESUMO

BACKGROUND: Demoralization is a psychological response that is frequently observed in patients with cancer or advanced diseases. It is affected by national characteristics, culture, disease characteristics and general conditions of the patient such as individual cultural features, nature of stress, personal expression preferences and social behavior. Compared with the results of previous studies on demoralization syndrome, patients with cancer in Taiwan exhibit a higher prevalence of demoralization. We aimed to investigate the prevalence of high demoralization and the changes in the level of demoralization in cancer patients during radiotherapy to explore the associated factors and the contributing factors to the high level of demoralization. METHODS: We used the Demoralization Scale-Mandarin Version to evaluate the demoralization level at six-time points in patients admitted for radiotherapy in a 3-month observational period. 101 patients allocated to three groups by cancer region completed the study. We applied the generalized estimating equation (GEE) to analyze the changes in the demoralization level among the three groups. The variables associated with the changes in the demoralization level were also investigated. RESULTS: In the analysis using univariate GEE, only patients in the chest and breast group exhibited significant changes at two different time points. The results obtained using multivariate GEE revealed that sociodemographic variables, stage of disease and use of surgery or chemotherapy had no impact on the changes in demoralization across three months. CONCLUSION: The demoralization level certainly fluctuated in an extremely high range. The higher prevalence of demoralized patients may indicate that if medical staff neglect the importance of demoralization, demoralized patients with cancer may not receive appropriate care.


Assuntos
Desmoralização , Neoplasias , Humanos , Estudos Longitudinais , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/radioterapia , Prevalência , Estresse Psicológico/psicologia
13.
Phys Med Biol ; 67(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-35912877

RESUMO

Objective.Combined proton-photon treatments, where most fractions are delivered with photons and only a few are delivered with protons, may represent a practical approach to optimally use limited proton resources. It has been shown that, when organs at risk (OARs) are located within or near the tumor, the optimal multi-modality treatment uses protons to hypofractionate parts of the target volume and photons to achieve near-uniform fractionation in dose-limiting healthy tissues, thus exploiting the fractionation effect. These plans may be sensitive to range and setup errors, especially misalignments between proton and photon doses. Thus, we developed a novel stochastic optimization method to directly incorporate these uncertainties into the biologically effective dose (BED)-based simultaneous optimization of proton and photon plans.Approach.The method considers the expected valueEband standard deviationσbof the cumulative BEDbin every voxel of a structure. For the target, a piecewise quadratic penalty function of the formbmin-Eb-2σb+2is minimized, aiming for plans in which the expected BED minus two times the standard deviation exceeds the prescribed BEDbmin.Analogously,Eb+2σb-bmax+2is considered for OARs.Main results.Using a spinal metastasis case and a liver cancer patient, it is demonstrated that the novel stochastic optimization method yields robust combined treatment plans. Tumor coverage and a good sparing of the main OARs are maintained despite range and setup errors, and especially misalignments between proton and photon doses. This is achieved without explicitly considering all combinations of proton and photon error scenarios.Significance.Concerns about range and setup errors for safe clinical implementation of optimized proton-photon radiotherapy can be addressed through an appropriate stochastic planning method.


Assuntos
Neoplasias , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Neoplasias/radioterapia , Órgãos em Risco , Fótons/uso terapêutico , Terapia com Prótons/métodos , Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos
14.
ACS Biomater Sci Eng ; 8(9): 3644-3658, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36000986

RESUMO

Radiotherapy (RT) is the primary standard of care for many locally advanced cancers. Often times, however, the efficacy of RT is limited due to radio-resistance that cancer cells develop. Photodynamic therapy (PDT) has gained importance as an alternative local therapy. Because its mechanism involves minimal acquired resistance, PDT is a useful adjunct to RT. This review discusses recent advances in combining RT with PDT for cancer treatment. In the first part of this review, we will discuss clinical trials on RT + PDT combination therapies. All these approaches suffer from the same inherent limitations as any current PDT methods; (i) visible light has a short penetration depth in human tissue (<∼10 mm), and (ii) it is difficult to illuminate the entire tumor homogeneously by external/interstitial laser irradiation. To address these limitations, scintillating nanoparticle-mediated RT-PDT approaches have been explored in which nanoparticles convert X-rays (RT) into visible light (PDT); high-energy X-rays can reach deep into the body to irradiate cancers uniformly and precisely. The second part of this review will discuss recent efforts in developing and applying nanoparticles for RT-PDT applications.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Fotoquimioterapia/métodos , Triazenos , Raios X
15.
Cancer Radiother ; 26(6-7): 955-961, 2022 Oct.
Artigo em Francês | MEDLINE | ID: mdl-36030189

RESUMO

Thanks to the success of checkpoint inhibitors, immunotherapy now plays a major role in the management of a large number of solid tumors, while the number of indications continues to grow and new combinations could, in the near future, further modify treatment standards. However, the response rates of immunotherapies as monotherapy are modest and their use is increasingly considered in combination with other cancer treatments (chemotherapy, surgery, radiotherapy or certain targeted therapies). Combinations with radiotherapy seem particularly attractive because there is a strong experimental rationale linking part of the efficacy of ionizing radiation to an induced stimulation of both of the innate and adaptive response. Many early phases and a number of large randomized combination trials have published efficacy and safety results, while important trials are still ongoing and will provide answers in the near future. This short review recalls the experimental biological rationale for immuno-radiotherapy and highlights some of the fundamental directions being explored, then presents the clinical efficacy and safety results available to date, those expected in the near future, and finally outlines the outlook in this rapidly evolving field.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Humanos , Imunoterapia/métodos , Neoplasias/radioterapia
16.
Cancer Radiother ; 26(6-7): 789-793, 2022 Oct.
Artigo em Francês | MEDLINE | ID: mdl-36031495

RESUMO

Paediatric radiotherapy differs greatly from its practice in adults mainly because of the age (median age 6 years), which poses the problem of irradiation of healthy tissues in a growing organism, causing sequelae, difficult compliance and management of parents. These particularities require a dedicated education and specific organisation that was set progressively concerning indications, quality control, exhaustive collection of native dosimetry, long-term follow-up and clinical and translational research, as well as accreditations to practice paediatric radiotherapy, in close collaboration with the French society of child and adolescent cancer and leukaemia (SFCE), under the aegis of the French group of paediatric radiotherapy (GFRP). This organization is a pioneer in the development of pediatric radiotherapy quality controls, which are becoming the European standard and in the collection of native dosimetry integrated with the follow-up of possible late-effects, constituting the most important international database.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Adolescente , Adulto , Criança , Bases de Dados Factuais , França , Humanos , Oncologia , Neoplasias/radioterapia
17.
J Hematol Oncol ; 15(1): 123, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045419

RESUMO

The vast majority of our knowledge regarding cancer radiobiology and the activation of radioresistance mechanisms emerged from studies using external beam radiation therapy (EBRT). Yet, less is known about the cancer response to internal targeted radionuclide therapy (TRT). Our comparative phosphoproteomics analyzed cellular responses to TRT with lutetium-177-labeled minigastrin analogue [177Lu]Lu-PP-F11N (ß-emitter) and EBRT (É£-rays) in CCKBR-positive cancer cells. Activation of DNA damage response by p53 was induced by both types of radiotherapy, whereas TRT robustly increased activation of signaling pathways including epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs) or integrin receptor. Inhibition of EGFR or integrin signaling sensitized cancer cells to radiolabeled minigastrin. In vivo, EGFR inhibitor erlotinib increased therapeutic response to [177Lu]Lu-PP-F11N and median survival of A431/CCKBR-tumor bearing nude mice. In summary, our study explores a complex scenario of cancer responses to different types of irradiation and pinpoints the radiosensitizing strategy, based on the targeting survival pathways, which are activated by TRT.


Assuntos
Neoplasias , Radioisótopos , Animais , Linhagem Celular Tumoral , Receptores ErbB , Integrinas , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radioisótopos/uso terapêutico
18.
Biomed Pharmacother ; 154: 113610, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36030591

RESUMO

Cancer is a devastating disease and is the second leading cause of death worldwide. Surgery, chemotherapy (CT), and/or radiation therapy (RT) are the treatment of choice for most advanced tumors. Unfortunately, treatment failure due to intrinsic and acquired resistance to the current CT and RT is a significant challenge associated with poor patient prognosis. There is an urgent need to develop and identify agents that can sensitize tumor cells to chemo-radiation therapy (CRT) with minimal cytotoxicity to the healthy tissues. While many recent studies have identified the underlying molecular mechanisms and therapeutic targets for CRT failure, using small molecule inhibitors to chemo/radio sensitize tumors is associated with high toxicity and increased morbidity. Natural products have long been used as chemopreventive agents in many cancers. Combining many of these compounds with the standard chemotherapeutic agents or with RT has shown synergistic effects on cancer cell death and overall improvement in patient survival. Based on the available data, there is strong evidence that natural products have a robust therapeutic potential along with CRT and their well-known chemopreventive effects in many solid tumors. This review article reports updated literature on different natural products used as CT or RT sensitizers in many solid tumors. This is the first review discussing CT and RT sensitizers together in cancer.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias , Radiossensibilizantes , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico
19.
JCO Glob Oncol ; 8: e2100358, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35960905

RESUMO

The discipline of radiation oncology is the most resource-intensive component of comprehensive cancer care because of significant initial investments required for machines, the requirement of dedicated construction, a multifaceted workforce, and recurring maintenance costs. This review focuses on the challenges associated with accessible and affordable radiation therapy (RT) across the globe and the possible solutions to improve the current scenario. Most common cancers globally, including breast, prostate, head and neck, and cervical cancers, have a RT utilization rate of > 50%. The estimated annual incidence of cancer is 19,292,789 for 2020, with > 70% occurring in low-income countries and low-middle-income countries. There are approximately 14,000 teletherapy machines globally. However, the distribution of these machines is distinctly nonuniform, with low-income countries and low-middle-income countries having access to < 10% of the global teletherapy machines. The Directory of Radiotherapy Centres enlists 3,318 brachytherapy facilities. Most countries with a high incidence of cervical cancer have a deficit in brachytherapy facilities, although formal estimates for the same are not available. The deficit in simulators, radiation oncologists, and medical physicists is even more challenging to quantify; however, the inequitable distribution is indisputable. Measures to ensure equitable access to RT include identifying problems specific to region/country, adopting indigenous technology, encouraging public-private partnership, relaxing custom duties on RT equipment, global/cross-country collaboration, and quality human resources training. Innovative research focusing on the most prevalent cancers aiming to make RT utilization more cost-effective while maintaining efficacy will further bridge the gap.


Assuntos
Braquiterapia , Neoplasias , Radioterapia (Especialidade) , Assistência Integral à Saúde , Humanos , Masculino , Neoplasias/epidemiologia , Neoplasias/radioterapia , Recursos Humanos
20.
Cancer Radiother ; 26(6-7): 962-967, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35989153

RESUMO

The importance of tumoral vascularization as a therapeutic target was first described in 1971 by Folkman. Anarchic vascularization in response to tumour hypoxia, especially mediated by vascular endothelial growth factor, represents a major target in the management of many cancers. The contribution of systemic anti-angiogenic treatments including humanized anti-VEGF monoclonal antibodies (bevacizumab) and tyrosine kinase inhibitors, whose effect on vascular normalization and correction of tumour hypoxia has been shown in preclinical studies to be enhancing the effect of radiotherapy. Early trials combining radiotherapy and antiangiogenics with a small number of patients have contradictory results and tend to put into perspective the opportunity that this synergistic association represents. The efficiency found must be tempered by some toxicity described, especially in association with high doses per fraction. The aim of this article is to present the main studies reporting the efficiency and safety of the combination of antiangiogenic drugs and radiotherapy, as well as the expected opportunities.


Assuntos
Neoplasias , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Bevacizumab/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases
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