The experimental models are of vital significance to provide information regarding biological as well as genetic factors that control the phenotypic characteristics of the disease and serve as the foundation for the development of rational intervention stratagem. This review highlights the importance of experimental models in the field of cancer management. The process of pathogenesis in cancer progression, invasion and metastasis can be successfully explained by employing clinically relevant laboratory models of the disease. Cancer cell lines have been used extensively to monitor the process of cancer pathogenesis process by controlling growth regulation and chemo-sensitivity for the evaluation of novel therapeutics in both in vitro and xenograft models. The experimental models have been used for the elaboration of diagnostic or therapeutic protocols, and thus employed in preclinical studies of bioactive agents relevant for cancer prevention. The outcome of this review should provide useful information in understanding and selection of various models in accordance with the stage of cancer.
Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.
Paclitaxel (PTX) is an effective anticancer agent used in the therapy of a wide variety of cancers. However, the drug is difficult to formulate due to its low solubility, and therefore, it is administered under slow infusion with castor oil/ethanol solution as surfactant that causes serious side effects. This investigation investigates leutinizing hormone releasing hormone (LHRH)-tethered nanparticulate system as modality for cancer-specific delivery of PTX and therefore minimizing the adverse effects.