Coralie Moncharmont

Targeting a cornerstone of radiation resistance: cancer stem cell.

In radiation oncology, cancer stem cells (CSCs) have become an important research field. In fact, it appears that most cancer types contain populations of cells that exhibit stem-cell properties. CSCs have the ability to renew indefinitely, which can drive tumor development and metastatic invasion. As those cells are classically resistant to conventional chemotherapy and to radiation therapy, they may contribute to treatment failure and relapse. Over past decades, preclinical research has highlighted that variations in the CSCs content within tumor could affect their radiocurability by interfering with mechanisms of DNA repair, redistribution in the cell cycle, tumor cells repopulation, and hypoxia. It is now possible to isolate particular cells expressing specific surface markers and thus better investigating CSCs pathways. Numerous inhibitory agents targeting these specific signaling pathways, such as Notch and Wnt/B-catenin, are currently evaluated in early clinical trials. By targeting CSCs, tumor radioresistance could be potentially overcome to improve outcome for patients with solid malignancies. Radiation therapy using ion particles (proton and carbon) may be also more effective than classic photon on CSCs. This review presents the major pathophysiological mechanisms involved in CSCs radioresistance and recent developments for targeted strategies.

Radiation-enhanced cell migration/invasion process: a review.

Radiation therapy is a keystone treatment in cancer. Photon radiation has proved its benefits in overall survival in many clinical studies. However, some patients present local recurrences or metastases when cancer cells survive to treatment. Metastasis is a process which includes adhesion of the cell to the extracellular matrix, degradation of the matrix by proteases, cell motility, intravasation in blood or lymphatic vessels, extravasation in distant parenchyma and development of cell colonies. Several studies demonstrated that ionizing radiation might promote migration and invasion of tumor cells by intricate implications in the micro-environment, cell-cell junctions, extracellular matrix junctions, proteases secretion, and induction of epithelial-mesenchymal transition. This review reports various cellular pathways involved in the photon-enhanced cell invasion process for which potential therapeutic target may be employed for enhancing antitumor effectiveness. Understanding these mechanisms could lead to therapeutic strategies to counter the highly invasive cell lines via specific inhibitors or carbon-ion therapy.

Facteurs de radiorésistance des cellules souches cancéreuses et perspectives de radiosensibilisation: l'exemple du glioblastome

Cancer stem cells are a subject of increasing interest in oncology. In particular, several data suggest that cancer stem cells are involved in the mechanisms of tumor radioresistance, and may explain the therapeutic failures after radiotherapy. Because of its poor prognosis and high recurrence rate after irradiation, glioblastoma model is often studied in the search for new radiosensitizers. There are several preclinical data suggesting that cancer stem cells could be a potential therapeutic target for improving the biological effectiveness of radiation therapy. Through the example of glioblastoma, we review the main signaling pathways involved in the mechanisms of radiation resistance of cancer stem cells and for which pharmacological targeting could potentially enhance tumor radiosensitivity.

Cisplatine ou carboplatine, telle est la question

Platine-based chemotherapy agents are major drugs in oncology and are currently used in most solid malignancies. Of these, cisplatin has been the most widely used over past years. Its efficacy and toxicity have been both well documented in the literature. Carboplatin has a rather different toxicity profile and seems to be better tolerated than cisplatin. This might potentially impact on quality of life. Carboplatin has been assessed for treatment of most malignancies in which cisplatin has demonstrated its efficacy. This paper aims at reviewing and comparing the current indications in terms of efficacy and toxicity of cisplatin and carboplatin. Although cisplatin has demonstrated its superiority over carboplatin for treatment of lung cancers and germ-cell tumors, the tolerance of carboplatin is better than that of cisplatin. This might be taken into account for patients treated with non-curative attempt. Further studies should compare both chemotherapy agents for quality of life. Of course, carboplatin remains widely used for patients who are contra-indicated for cisplatin.

Ultraviolet recall dermatitis reaction with sorafenib

SummaryPurpose Recall dermatitis is a rare and poorly understood drug-related event. Activated by exposure to sunlight or Ultraviolet (UV), drug-related phototoxic reactions have been reported with conventional chemotherapy agents or antibiotics. Methods Here, we report the first case of acute dermatologic photo-induced recall reaction secondary to sorafenib in a patient with renal cell carcinoma. Results Four weeks after stopping sorafenib, a patient with renal cell carcinoma developed an acute erythematous and papulomatous eruption restricted to the hands after prolonged solar exposure. The erythematous region was very well demarcated, mimicking the cutaneous syndrome that the patient had presented at time he was receiving sorafenib. Conclusions The suppression of the phototoxic reaction by corticosteroids strongly suggests that the immune system may have an important function in photo-recall reactions.

Mélanomes du tractus génital féminin : état des lieux

Melanoma of the female genital tract is a rare location (less than 2% of melanomas all sites combined). These cancers have a very poor prognosis, due to the delay in diagnosis. Vulvar location is about 1% of melanomas then the vaginal location, uterine and ovarian. There is no consensus to date regarding their care, due to the rarity of the lesions. Their treatment must however be based on the current data concerning gynaecological cancers as well as standard management of cutaneous melanoma. The treatment is often based on conservative surgery, because radical resection does not improve survival. For the vulva and vagina, reconstructive surgery is possible. Treatment is sometimes supplemented by chemotherapy or radiotherapy, which could improve local control. The interest in the use of targeted therapy in these locations is not well known because of their rarity, but the study of genes c-Kit and BRAF provides new prospects for treatment. The objective of this review is to describe and report the current state of knowledge about gynaecologic melanomas.

Curative-Intended Treatment of Squamous Cell Anal Carcinoma in Elderly Adults

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Mise en place d'une étude pilote de sensibilisation au réentraînement à l'activité physique dans deux populations sélectionnées atteintes d'un cancer du sein

The purpose of this study is to measure the impact of an educational program to raise awareness of the increased spending energy in two different population of patients with breast cancer by using the questionnaire POPAQ (Population Physical Activity Questionnaire). This is a prospective study including two groups of 15 consecutive breast cancer patients (≤ 50 years Group 1 and Group 2 > 50 and < 70 years) followed in the department of radiotherapy at the Institute of Cancer of the Loire from January to July 2011. A questionnaire of physical activity assessment was used at two different times before the diagnosis/treatment of breast cancer (t0) and at 6 months (t6) to measure the impact of the awareness method. Comparison of different measures of daily energy expenditure (t0) between groups 1 and 2 was statistically significant (1,1803 and 9434 kJ/24 h, respectively, p = 0.0005). Daily energy expenditure of professional activity was statistically different between the two groups (1437 and 457 kJ/24 h, in groups 1 and 2, respectively; p = 0.003). Between t0 and t6, we observed a significant decrease in total energy consumption in group 1 (1,1803 to 1,0876 kJ/24 h) while there was no significant change between the group 2, except energy expended at rest (basal metabolism). There were differences in daily energy expenditure based on age may influence behavioral patterns deal with energy expenditure in physical activities. Tomorrows challenges are to provide re-entrainment programs tailored to targeted populations.

Carbon ion irradiation withstands cancer stem cells’ migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

Cancer Stem Cells (CSCs) in Head and Neck Squamous Cell Carcinoma (HNSCC) have extremely aggressive profile (high migratory and invasive potential). These characteristics can explain their resistance to conventional treatment. Efficacy of photon and carbon ion irradiation with addition of cetuximab (5 nM) is studied on clonogenic death, migration and invasion of two HNSCC populations: SQ20B and SQ20B/CSCs. SQ20B express E-cadherin and overexpress EGFR while SQ20B/CSCs express N-cadherin and low EGFR. Cetuximab strongly inhibits SQ20B proliferation but has no effect on SQ20B/CSCs. 2 Gy photon irradiation enhances migration and invasiveness in both populations (p < 0.05), while cetuximab only stops SQ20B migration (p < 0.005). Carbon irradiation significantly inhibits invasion in both populations (p < 0.05), and the association with cetuximab significantly inhibits invasion in both populations (p < 0.005). These results highlight CSCs characteristics: EGFRLow, cetuximab-resistant, and highly migratory. Carbon ion irradiation appears to be a very promising therapeutic modality counteracting migration/invasion process in both parental cells and CSCs in contrast to photon irradiation.

Chemotherapy Regimen in Nonagenarian Cancer Patients: A Bi-Institutional Experience

Background: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. Methods: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. Results: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. Conclusion: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.