Abstract
Advanced cancer is still considered an incurable disease because of its metastatic spread to distal organs and progressive gain of chemoresistance. Even though considerable treatment progress and more effective therapies have been achieved over the past years, recurrence in the long-term and undesired side effects are still the main drawbacks of current clinical protocols. Moreover, a majority of chemotherapeutic drugs are highly hydrophobic and need to be diluted in organic solvents, which cause high toxicity, in order to reach effective therapeutic dose. These limitations of conventional cancer therapies prompted the use of nanomedicine, the medical application of nanotechnology, to provide more effective and safer cancer treatment. Potential of nanomedicines to overcome resistance, ameliorate solubility, improve pharmacological profile, and reduce adverse effects of chemotherapeutical drugs is thus highly regarded. Their use in the clinical setting has increased over the last decade. Among the various existing nanosystems, nanoparticles have the ability to transform conventional medicine by reducing the adverse effects and providing a controlled release of therapeutic agents. Also, their small size facilitates the intracellular uptake. Here, we provide a closer review of clinical prospects and mechanisms of action of nanomedicines to overcome drug resistance. The significance of specific targeting towards cancer cells is debated as well.
Highlights
According to the World Health Organization, cancer is the second leading cause of death globally, with estimated 9.6 million deaths in 2016
Closer understanding of the mechanisms involved in drug resistance is needed in order to achieve better outcomes in cancer treatment
Even though the use of active targeting does not seem to be able to significantly change the accumulation of NPs by EPR effect at the tumour sites in vivo, the interaction between a ligand and a receptor can be used to improve the internalization of the nanomedicine in tumour cells at the tumour site[75]
Summary
According to the World Health Organization, cancer is the second leading cause of death globally, with estimated 9.6 million deaths in 2016. CRLX101 is a polymer - drug conjugate formulation of camptothecin, a topoisomerase I inhibitor, and a cyclodextran-PEG polymer which is being studied alone and in combination with other drugs in numerous phase I and II clinical trials in the treatment of lung cancers, gynecological malignancies, and solid tumours[65].
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