Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by the rapid proliferation of mutagenic hematopoietic progenitors in the bone marrow. Conventional therapies include chemotherapy and bone marrow stem cell transplantation; however, they are often associated with poor prognosis. Notably, growth hormone-releasing hormone (GHRH) receptor antagonist MIA-602 has been shown to impede the growth of various human cancer cell lines, including AML. This investigation examined the impact of MIA-602 as monotherapy and in combination with Doxorubicin on three Doxorubicin-resistant AML cell lines, KG-1A, U-937, and K-562. The in vitro results revealed a significant reduction in cell viability for all treated wild-type cells. Doxorubicin-resistant clones were similarly susceptible to MIA-602 as the wild-type counterpart. Our in vivo experiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602.

Controlled release nanoplatforms for three commonly used chemotherapeutics.

In order to combat an evolving, multidimensional disease such as cancer, research has been aimed at synthesizing more efficient and effective versions of popular chemotherapeutic drugs. Despite these efforts, there remains a necessity for the development of suitable delivery vehicles that can both harness the chemotherapeutic effects meanwhile reducing some of the known issues when using these drugs such as unwanted side-effects, acquired drug resistance, and associated difficulties with drug delivery. Synthetic drug discovery approaches focusing on modification of the native structure of these chemotherapeutic drugs often face challenges such as loss of efficacy, as well as a potential worsening of side-effects. Synthetic chemists are then left with increasingly narrow choices for possible chemistry they could implement to achieve the desired therapy. The emergence of targeted therapies using controlled-release nanomaterials can provide many opportunities for conventional chemotherapeutic drugs to be delivered to specific target sites, ultimately leading to reduced side-effects and improved efficacy. Logically, it may prove advantageous to consider nano-delivery systems as a likely candidate for circumventing some of the barriers associated with creating viable drug therapies. In this review, we summarize controlled release nanoformulations of the three most widely used and approved chemotherapeutics, doxorubicin, paclitaxel, and cisplatin as an alternative therapeutic approach against different cancer types.