Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: The use of octreotide and chloroquine in oncology

Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic use of octreotide is restricted primarily to the management of acromegaly and neuroendocrine tumors, both of which are rare medical conditions. Similarly, chloroquine is used mainly for the treatment of malaria, which is designated as a rare disease in Western countries. This limited exploitation contradicts the experimental findings of numerous studies outlining the possible expansion of the use of octreotide to include the treatment of common human malignancies and the repositioning of chloroquine in oncology. Herein, we review the current knowledge on the antitumor function of these two agents stemming from preclinical or clinical experimentation. In addition, we present in silico evidence on octreotide potentially binding to multiple Wnt-pathway components. This will hopefully aid in the design of new efficacious anticancer therapeutic regimens with minimal toxicity, which represents an enormous unmet demand in oncology. © 2019 Papanagnou et al

Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: the use of octreotide and chloroquine in oncology

Panagiota Papanagnou,1,* Georgios E Papadopoulos,2,* Theodora Stivarou,3 Anastasios Pappas1 1Department of Urology, Agios Savvas Cancer Hospital, Athens 11522, Greece; 2Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41500, Greece; 3Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute, Athens, Greece *These authors contributed equally to this work Abstract: Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic use of octreotide is restricted primarily to the ma­nagement of acromegaly and neuroendocrine tumors, both of which are rare medical conditions. Similarly, chloroquine is used mainly for the treatment of malaria, which is designated as a rare disease in Western countries. This limited exploitation contradicts the experimental findings of numerous studies outlining the possible expansion of the use of octreotide to include the treatment of common human malignancies and the repositioning of chloroquine in oncology. Herein, we review the current knowledge on the antitumor function of these two agents stemming from preclinical or clinical experimentation. In addition, we present in silico evidence on octreotide potentially binding to multiple Wnt-pathway components. This will hopefully aid in the design of new efficacious anticancer therapeutic regimens with minimal toxicity, which represents an enormous unmet demand in oncology. Keywords: drug repositioning, pleiotropy, neuroendocrine tumors, lysosomotropic agent, cancer, dockin

Marketed drugs used for the management of hypercholesterolemia as anticancer armament

Panagiota Papanagnou,1 Theodora Stivarou,2 Ioannis Papageorgiou,1 Georgios E Papadopoulos,3 Anastasios Pappas1 1Department of Urology, Agios Savvas Cancer Hospital, Athens, Greece; 2Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute, Athens, Greece; 3Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece Abstract: The design of novel pharmacologic agents as well as their approval for sale in markets all over the world is a tedious and pricey process. Inevitably, oncologic patients commonly experience unwanted effects of new anticancer drugs, while the acquisition of clinical experience for these drugs is largely based on doctor–patient partnership which is not always effective. The repositioning of marketed non-antineoplastic drugs that hopefully exhibit anticancer properties into the field of oncology is a challenging option that gains ground and attracts preclinical and clinical research in an effort to override all these hindrances and minimize the risk for reduced efficacy and/or personalized toxicity. This review aims to present the anticancer properties of drugs used for the management of hypercholesterolemia. A global view of the antitumorigenicity of all marketed antihypercholesterolemic drugs is of major importance, given that atherosclerosis, which is etiologically linked to hypercholesterolemia, is a leading worldwide cause of morbidity and mortality, while hypercholesterolemia and tumorigenesis are known to be interrelated. In vitro, in vivo and clinical literature data accumulated so far outline the mechanistic basis of the antitumor function of these agents and how they could find application at the clinical setting. Keywords: antihypercholesterolemic agents, cancer, synergism, repurposin

Marketed drugs used for the management of hypercholesterolemia as anticancer armament

The design of novel pharmacologic agents as well as their approval for sale in markets all over the world is a tedious and pricey process. Inevitably, oncologic patients commonly experience unwanted effects of new anticancer drugs, while the acquisition of clinical experience for these drugs is largely based on doctor–patient partnership which is not always effective. The repositioning of marketed non-antineoplastic drugs that hopefully exhibit anticancer properties into the field of oncology is a challenging option that gains ground and attracts preclinical and clinical research in an effort to override all these hindrances and minimize the risk for reduced efficacy and/or personalized toxicity. This review aims to present the anticancer properties of drugs used for the management of hypercholesterolemia. A global view of the antitumorigenicity of all marketed antihypercholesterolemic drugs is of major importance, given that atherosclerosis, which is etiologically linked to hypercholesterolemia, is a leading worldwide cause of morbidity and mortality, while hypercholesterolemia and tumorigenesis are known to be interrelated. In vitro, in vivo and clinical literature data accumulated so far outline the mechanistic basis of the antitumor function of these agents and how they could find application at the clinical setting. © 2017 Papanagnou et al