Cancers are heterogeneous at the cell level, and the mechanisms leading to cancer heterogeneity could be clonal evolution or cancer stem cells. Cancer stem cells are resistant to most anti-cancer treatments and could be preferential targets to reverse this resistance, either targeting stemness pathways or cancer stem cell surface markers. Gold nanoparticles have emerged as innovative tools, particularly for photo-thermal therapy since they can be excited by laser to induce hyperthermia. Gold nanoparticles can be functionalized with antibodies to specifically target cancer stem cells. Preclinical studies using photo-thermal therapy have demonstrated the feasibility of targeting chemo-resistant cancer cells to reverse clinical chemoresistance. Here, we review the data linking cancer stem cells and chemoresistance and discuss the way to target them to reverse resistance. We particularly focus on the use of functionalized gold nanoparticles in the treatment of chemo-resistant metastatic cancers.

Breast cancer brain metastases are a challenging daily practice, and the biological link between gene mutations and metastatic spread to the brain remains to be determined. Here, we performed a meta-analysis on genomic data obtained from primary tumors, extracerebral metastases and brain metastases, to identify gene alterations associated with metastatic processes in the brain. Articles with relevant findings were selected using Medline via PubMed, from January 1999 up to February 2022. A critical review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement (PRISMA). Fifty-seven publications were selected for this meta-analysis, including 37,218 patients in all, 11,906 primary tumor samples, 5541 extracerebral metastasis samples, and 1485 brain metastasis samples. We report the overall and sub-group prevalence of gene mutations, including comparisons between primary tumors, extracerebral metastases and brain metastases. In particular, we identified six genes with a higher mutation prevalence in brain metastases than in extracerebral metastases, with a potential role in metastatic processes in the brain: ESR1, ERBB2, EGFR, PTEN, BRCA2 and NOTCH1. We discuss here the therapeutic implications. Our results underline the added value of obtaining biopsies from brain metastases to fully explore their biology, in order to develop personalized treatments.

Massive Open Online Courses (MOOCs) are gaining popularity in education while classroom lectures are being deserted, especially after COVID-19 pandemic. Their added value in teaching undergraduate medical students remains to be confirmed.

Docetaxel is a major anticancer drug that can induce hypersensitivity reactions leading to deleterious treatment interruptions. Blood hypereosinophilia could be a biological sign, potentially lethal, of delayed visceral hypersensitivity reactions. We hypothesized this biological event is probably underreported. In this prospective observational study, we followed up 149 patients treated with docetaxel monotherapy for breast or lung cancer. For each patient, blood eosinophil counts were recorded during docetaxel treatment and up to 3 months after the end of docetaxel treatment. For all patients, blood eosinophil counts significantly increased under docetaxel chemotherapy (P < 0.01). Seven percent had persistent eosinophilia after the end of treatment. Four patients had blood eosinophil counts over 1000/mm³ with severe cardiac, cutaneous and digestive toxicities, and docetaxel imputability was confirmed using drug‐imputability scales. For two of these four patients, tissue biopsies were performed during the time of hypereosinophilia and of severe toxicities. Specific immunostainings and electron microscopy found numerous degranulating mast cells and eosinophils. Our study demonstrated that eosinophilia is frequent under docetaxel and could lead to severe complications, implicating eosinophils and mast cells, and possibly IgE. One way of treating hypersensitivity reactions could be by targeting IgEs with omalizumab, an anti‐IgE monoclonal antibody approved for the treatment of severe allergic asthma, and successfully used in food and poison‐induced anaphylactic reactions.

Hypereosinophilia, defined by an absolute eosinophil count of more than 1500/mm3, is rarely observed in patients treated for cancer, and rarely imputable to anti-cancer agents. Drug-induced hypereosinophilia usually appears within a few weeks of the start of treatment and resolves after discontinuation of the medication. We report here a first case of hypereosinophilia with digestive allergic reaction imputable to docetaxel in a woman treated for breast cancer. This patient, with a history of childhood atopic dermatitis and asthma, underwent surgery for breast lobular carcinoma, followed with chemotherapy including 3 cycles of the FEC100 protocol and 3 cycles of docetaxel. Ten days after the second cycle of docetaxel, she had abdominal pain with diarrhea, which increased after the third cycle of docetaxel at the same dose. The blood eosinophil count increased up to 4685/mm3 at day 92. All biological tests were normal, except elevated seric IgE. The systematic biopsies of the upper and lower digestive tract showed diffuse edema of the lamina propria, lymphocytic infiltrate and CD117-expressing cells both in the epithelium and in the lamina propria. Electron microscopy showed a large number of degranulating mast cells, while the number of tissue eosinophils was small. The blood eosinophil count decreased after day 96, three months after the last injection of docetaxel. After day 182, the hypereosinophilia and symptoms resolved. This spontaneous evolution, the history of atopic dermatitis and asthma, and the negativity of all biological tests performed led us to hypothesize a diagnosis of a systemic digestive Type 1 drug-induced hypersensitivity reaction. Using two validated pharmacovigilance scales, we found that docetaxel had the highest imputability score compared to the other drugs. Recognition of allergic reactions imputable to docetaxel is important because it requires the drug to be discontinued. In the difficult setting of anti-cancer treatment, if reintroduction of the drug is needed, a close collaboration between oncologists, gastroenterologists and allergologists is required.