Small-cell lung cancers (SCLC) are aggressive malignancies, however, characterized by high primary chemosensitivity. Unfortunately, for the vast majority of patients, relapse is the rule with emergence of secondary resistance mechanisms. In the era of molecular targeted therapies, characterization of a number of molecular abnormalities has encouraged implementation of several clinical trials. This literature review summarizes the various pharmacological approaches used in SCLC to improve survival in localized and extensive forms of the disease. Initial trials with molecular targeted therapies have not been able to improve clinical outcome compared to the standard etoposide-cisplatin chemotherapy regimen in extensive forms. However, new targets continue to be identified and many treatments are currently being assessed, including blockade of angiogenesis, signal transduction, cell cycle or induction of apoptosis.

This research studies social representations of cancer and chemotherapy with patients (N = 62) and of oncologists (N = 26) in a medical oncology unit. The collection of the data was made from free association tasks (concerning cancer and chemotherapy) and attitude questions concerning chemotherapy. Patients also had to produce representations "for" oncologists and conversely. Results indicate a variety of representations marked by the status of sample (patients versus oncologists). The stressful component of the disease is very present. Contrary to the patients, oncologists seize relatively well the representation, which the patients have of concerning cancer and chemotherapy. Patients' representations are connected with phenomena of belief that give evidence for some process of anticipation and expectation linked to the experience of illness and testify the emotional charge related to it. The study of the representations is particularly relevant to highlight the psychosocial stakes associated with the therapeutic situation.

Some general and specific, statutory, clinical and biological parameters have to be taken into account before beginning chemotherapy in colorectal cancer to ensure maximal safety. Statutorily the prescription is reserved to specialised or competent physicians in oncology in some accredited institutions. It is essential to conform to indications, contraindications and posology, and to have a good knowledge of safety measures, drug interactions and side effects. Patients, family members and general practitioners should be informed about side effects, without forgetting some thematics (sexuality, fertility, contraception, vaccines, driving). This information should be simple, adapted and "reassuring", but should focus on symptoms indicating a serious toxic side effect. The message can be optimized by nurse consultation, transmission of the individualized care plan and linkage notebook, such as oral chemotherapies (capecitabine, UFT). The computerized and standardized prescription is done after infusion line inspection, clinical examination (global health status, nutritional status and buccodental status) and review of relevant pathological, radiological and biological data. Management of side effects includes patient education, appropriate premedication and prescription of prophylactic supportive care. Some specific preventive measures can attenuate the cutaneous side effects of EGFR inhibitors and the oxaliplatine-induced sensory neurotoxicity. Life expectancy, comorbidities, level of dependence, and if possible the comprehensive geriatric assessment should be taken into account for elderly patients. Prescription should be individualized and adapted to liver biology (irinotecan), kidney function (capecitabine and raltitrexed) and cardiovascular status (bevacizumab, 5-FU, capecitabin). Some molecular biologic prerequisites are indicated: detection of tumor KRAS-BRAF mutation before anti-EGFR and tumor microsatelliteinstability status before 5-FU in stage II cancers. Clinical relevance of others pretherapeutic molecularparameters are still being evaluated: UGT1A1 genotyping before irinotecan and detection of dihydropyrimidine dehydrogenase deficiency before fluoropyrimidines.

Nausea and emesis are one of the most feared secondary effect of chemotherapy. The development of antiemetic therapies has increased after the introduction of cisplatin, a cytotoxin with the highest emetic potential. Chemotherapy-induced nausea and vomiting (CINV) have been classified into acute, delayed and anticipatory based on the time of onset. According to the percentage of nausea and emesis without any antiemetic treatment, chemotherapy is divised into highly, moderate, low and very low emetic potential. The discovery of emetics stimuli neurotransmitters and their receptors has led to the introduction of new molecules which associated with steroids have prevented nausea and vomiting chemotherapy-induced for 70 to 80% of the patients receiving chemotherapy with high emetic potential. Numerous studies have evaluated the various antiemetics and recommendations were issued by learned societies in US and Europe. This text discusses the physiopathology of nausea and vomiting, the development of anti-emetics and the new discovered antiemetics. Finally, a synthesis of the recommandations from the guidelines developed by the Multinational Association of Supportive Care in Cancer (MASCC), the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) is presented.

In the 1980s, progress in molecular biology enabled the manipulation and cloning of antibody fragments as functional scFv (single chain Fv). Because of their small size and relative ease of expression, scFv opened the road for new medical and biotechnological applications. scFvs can be easily expressed and targeted to different cellular compartments (cytosol, nucleus, endoplasmic reticulum, mitochondria, inner surface of the plasma membrane, etc.), using specific signals to target or retain them in a given compartment. Recombinant antibodies can thus be used as intracellular antibodies (intrabody) to neutralize, disrupt or track endogenous antigen. Intrabodies not only represent new tools for fundamental research to study the dynamics of endogenous proteins, but may also bring interesting options for applied research in terms of intracellular immunization for therapeutic use.

The first treatment ever by radio-immunotherapy (RIT) was performed by William H. Beierwaltes in 1951 and was a success. Fifty years later, the main question is to find ways of extending the success of radiolabelled anti-CD20 antibodies in indolent non-Hodgkin's lymphoma to other forms of cancer. Solid tumours are much more radioresistant than lymphomas, but they respond to RIT if the lesions are small. Clinical situations of residual or minimal disease are thus the most likely to benefit from RIT in the adjuvant or consolidation settings. For disseminated disease, like leukemias or myelomas, the problem is different: beta- particles emitted by the radioactive atoms classically used for cancer treatment (iodine-131 or yttrium-90) disperse their energy in large volumes (ranges 1 mm to 1 cm) and are not very effective against isolated cells. Advances in RIT progress in two directions. One is the development of pretargeting strategies in which the antibody is not labelled but used to provide binding sites to small molecular weight radioactivity vectors (biotin, haptens). These techniques have been shown to increase tumour to non-target uptake ratios and anti-tumour efficacy has been demonstrated in the clinic. The other approach is the use of radionuclides adapted to the various clinical situations. Lutetium-177 or copper-67, because of the lower energy of their emission, their relatively long half-life and good gamma emission, may significantly improve RIT efficacy and acceptability. Beyond that, radionuclides emitting particles such as alpha particles or Auger electrons, much more efficient to kill isolated tumour cells, are being tested for RIT in the clinic. Finally, RIT should be integrated with other cancer treatment approaches in multimodality protocols. Thus RIT, now a mature technology, should enter a phase of well designed and focused clinical developments that may be expected to afford significant therapeutic advances.

EGFR receptor inhibitors are used for the treatment of a number of solid tumors. Their cutaneous toxicity is a specific and frequent side effect that has shown to be correlated to the antitumoral effect. Here, we present an overview of the cutaneous manifestations and management of EGF receptor inhibitors toxicity.

Sorafenib has been approved for use in the treatment of metastatic renal cell carcinoma. Cutaneous side-effects are common, including rash, hand-foot syndrome, alopecia, pruritus, dry skin and erythema. We report an original unexpected cutaneous effect: multiple keratoacanthomas. In the light of a literature review of drug-induced keratoacanthomas, we discuss the potential underlying physiopathological mechanism.

Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer. Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer. Literature review reveals a number of different experiences on feasibility of this technique, but scientific evidence of current studies remains poor. Much more research is still required to elucidate unanswered questions. Before this technique can be routinely used, some controversial aspects have to be defined: which drug is the best to deliver and at what temperature, is it necessary to use mono- or poly-chemotherapy regimens, which is the time-point for HIPEC in the natural history of ovarian cancer: at front-line therapy, at interval debulking following initial neo-adjuvant chemotherapy, at consolidation following front-line therapy, or at the time of recurrence. Nevertheless, we must not forget that the most important issue in ovarian cancer prognosis is maximal cytoreductive surgery, with no residual disease at completion of initial surgery.

In spite of the great advances made on the knowledge of cancer etiology and the significant breakthroughs in terms of treatment, complete remission is obtained in only around half of cancer patients. In fact, therapies that appear successful for some cancers are totally unfruitful for others, and some cancer types still remain incurables. In order to develop new therapies suitable to these tenacious cancers, we need to renew our view on cancer and to revise some old paradigms and "false friends" that can hide unexpected new therapeutic targets. A good example of these paradigms is the role of the cell stress response in tumor progression. Indeed, a number of studies has been devoted to the pivotal tumor suppressor function of some players of this response, of which the p53 protein is the best example. Nevertheless, during tumor progression and metastasis, the cancer cell faces many stresses imposed by tumor microenvironment and its survival will be conditioned by an efficient cell stress response. This review is consecrated to the role played by a pivotal actor of the cell stress response, the p8 protein, during carcinogenesis. We will recapitulate the data available on its different cell functions and the assets p8 confer to the cancer cell in terms of growth, drugs resistance and metastasis formations.

Intraperitoneal chemotherapy is a very attractive therapeutic alternative in the treatment of advanced ovarian carcinoma, due to its intraperitoneal spreading. Pharmacokinetic rational was described 30 years ago: a drug administered within the peritoneal cavity diffuse through the peritoneum towards the plasmatic compartment, depending on both its molecular weight and its lipid solubility. A slow output of the drug from the peritoneal cavity and a high plasma clearance are associated with a great pharmacokinetic advantage, illustrated by the area under the concentration time curve ratio. Then it is possible to increase the amount of drug directly delivered at the tumor site, while controlling the systemic toxicity. The agent administered in a large fluid volume come into direct contact with the tumor nodules, into which it penetrates from the free surface while it also reaches them by blood flow. The peripheral penetration being however limited to the first cellular layers, this way of delivery is interesting only for small residual disease. The most active drugs in the treatment of ovarian cancer, paclitaxel and platinum agents, are particularly convenient for this way of administration. The most optimal administration modality still remains to be defined and the development of the targeted therapies still opens new perspectives.

Some nucleoside analogs display significant activity against malignancies (gemcitabine, cytarabine) or viruses (ddl, ddC, AZT) by interfering with DNA synthesis. However, their use is limited by their relatively poor intracellular diffusion, rapid metabolism and induction of resistance. We have discovered that linking nucleoside analogs to squalene produces amphiphilic molecules that self-organize in water as nanoassemblies of 100-300 nm, irrespective of the nucleoside analog used. Gemcitabine nanoassemblies exhibited far greater activity than free gemcitabine against both subcutaneously grafted solid tumors (L1210 and P388) and aggressive metastatic leukemia (leukemia L1210 wt, P388 and RNK-16 LGL). Likewise, squalenated ddI and ddC nanoassemblies were more efficient than free ddI and ddC against HIV-infected lymphocytes. It is of prime importance to unravel the supramolecular organization of these nanoassemblies. For example, it has been shown that squalenated gemcitabine nanoassemblies form inverted hexagonal phases.