Novel Approaches for Targeted Cancer Therapy

Abstract

The clinical use of chemotherapeutic agents against malignant tumors is successful in many cases but suffers from major drawbacks. One drawback is lack of selectivity, which leads to severe side effects and limited efficacy; and another is the emergence/selection of drug-resistance. To limit non-specific toxicity and to improve the efficiency of cancer therapy, "tumor markers", which are proteins generally overexpressed on the surface of tumor cells, can be selectively targeted. Growth factor receptors are one of the most extensively studied tumor markers. The implication of growth factor receptors in the pathogenesis and evolution of cancer has clearly been established and therefore, provides a rationale for therapeutic intervention. The targeting of cytotoxic substances to tumor markers with "magic bullets" is an old idea that raised high expectations but also disappointment. Over the past decade, newly gained understanding of mechanisms for targeted therapy have brought new hopes. Pharmacological agents that selectively target and block the action of growth factors and their receptors have been attempted, such as monoclonal antibodies (mAbs) (whole molecule or fragments), bispecific antibodies, mAbs conjugated to drugs, toxins or radioisotopes, small peptidic and peptidomimetic molecules in free form or conjugated to drugs, anti-sense oligonucleotides, immunoliposomes-encapsulated drugs, and small molecule inhibitors. This review will focus on current developments of selective targeting and bypassing drug resistance in the management of growth factor receptor-overexpressing tumors.

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

“…The present major treatment modalities for cancer include chemotherapy, surgery and radiation therapy (4)(5)(6). In recent years immunotherapy has also been pursued in the management of cancer (7).…”

“…In recent years immunotherapy has also been pursued in the management of cancer (7). Chemotherapy is one of the most effective treatments available for cancer (4)(5)(6). New drugs and therapeutic strategies are continuously being researched and developed, but the current status of chemotherapy is far from satisfactory (8).…”

Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound

“…Some of the current targeted therapies attempt to localise drugs to cancer cells based on overexpression of epidermal growth factor receptors (EGFR) (Mendelsohn and Baselga, 2000) or angiogenesis (Carter, 2001). Antibodies, inhibitors, antisense therapy and gene therapy are also among a few strategies that have gained momentum (Guillemard and Saragovi, 2004). Many of these strategies have now reached clinical trials; however, these methods are still limited by issues including low potency, delivery complications, multi-drug resistance, side effects, collateral damage (Tattersall and Clarke, 2003) or incomplete success (Lynch et al, 2004).…”

Advances of Cancer Therapy by Nanotechnology

“…A variety of targeting ligands, including antibodies, antibody fragments, peptides, growth factors, and aptamers (64), have been used to facilitate the uptake of carriers into target cells (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76).…”