Abstract
Cancer is a multifactorial disease and is one of the leading causes of death worldwide. The contributing factors include specific genetic background, chronic exposure to various environmental stresses and improper diet. All these risk factors lead to the accumulation of molecular changes or mutations in some important proteins in cells which contributes to the initiation of carcinogenesis. Chemotherapy is an effective treatment against cancer but undesirable chemotherapy reactions and the development of resistance to drugs which results in multi-drug resistance (MDR) are the major obstacles in cancer chemotherapy. Strategies which are in practice with limited success include alternative formulations e.g., liposomes, resistance modulation e.g., PSC833, antidotes/toxicity modifiers e.g., ICRF-187 and gene therapy. Targeted therapy is gaining importance due to its specificity towards cancer cells while sparing toxicity to off-target cells. The scope of this review involves the various strategies involved in targeted therapy like-monoclonal antibodies, prodrug, small molecule inhibitors and nano-particulate antibody conjugates.
Highlights
Cancer is the second leading cause of deaths all over the world
Chemotherapy, and irradiation are the mainstream therapeutic approaches for cancer, chemotherapy being an important component of treatment for cancer patients
Antibody directed enzyme prodrug therapy (ADEPT) uses a conjugate which consists of tumor specific antibody linked to a drug-activating enzyme which when administered systemically targets tumor tissues
Summary
Cancer is the second leading cause of deaths all over the world. Globally 7.6 million deaths are caused by cancer which represents 13% of all global deaths [1]. The important aspect of prodrug cancer therapy is to deliver drug-activating enzyme or gene or functional protein to tumor tissues, followed by systemic administration of a prodrug [2]. Antibody directed enzyme prodrug therapy (ADEPT) uses a conjugate which consists of tumor specific antibody linked to a drug-activating enzyme which when administered systemically targets tumor tissues. This targeted enzyme which is localized on the tumor surface, converts the systemically administered nontoxic prodrug into a toxic drug resulting in cytotoxic effects in tumor cells [12, 35,36,37,38,39,40]. The main problem being the immunogenicity of the antibody-enzyme conjugate, which limits multiple cycles of its application this can be overcome with the use of humanized proteins and concomitant administration of immunosuppression [35]
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