Prolanta - Ovarian Cancer - Oncolix (pharma)

 Blogger's Note:  'About Us' section is typically a 'forward-thinking' statement by the manufacturer - clinical trials will determine the results

Prolanta - Ovarian Cancer


 Ovarian Cancer
    Ovarian Cancer Monotherapy
    Ovarian Cancer Combination Therapy

 Breast Cancer
    Breast Cancer Monotherapy
    Breast Cancer Combination Therapy

About Us

Oncolix, Inc. (Oncolix) is a clinical-stage bio-pharmaceutical company based in Houston, Texas. The company is developing Prolanta™, a targeted therapeutic protein for the treatment of ovarian and breast cancer. Prolanta is an antagonist of the human prolactin receptor, blocking the effects of human prolactin.  There is substantial scientific evidence that human prolactin is associated with the growth of certain gynecological cancers as well as resistance to platinum and taxane therapies.  By blocking the effects of prolactin,Prolanta has demonstrated a high level of efficacy in ovarian and breast cancer models.

Our initial focus is ovarian cancer, an Orphan Drug indication where there is a significant unmet medical need.  The first clinical trial of Prolanta to treat ovarian cancer is anticipated to begin in 2013. The preclinical testing required prior to the first-in-human clinical trial was completed in 2011, and the IND was cleared by the FDA in 2012.

Prolactin is mainly synthesized and secreted by lactotroph cells in the anterior pituitary gland, but is also produced at sites outside the pituitary gland, such as mammary gland, ovary, uterus, prostate, lymphocytes, brain, and several types of tumor cells.  This extra-pituitary prolactin can act as a tumor growth factor in an autocrine-paracrine fashion, both on the tumor cells that secrete prolactin (autocrine) as well as on nearby cells (paracrine).

Prolactin binds with its cell surface receptor through dimerization, activating various proliferation and chemo-resistance pathways.  Prolanta is an analogue to prolactin, with a single amino acid substitution mutation at position 129 to create a receptor-specific antagonist (also referred to as G129R).  This glycine to arginine substitution interferes with the binding of the mutated ligand at the second receptor site, thereby disrupting dimerization of the receptors necessary for activation.

As illustrated in the following figure, prolactin binds to two receptors and initiates various growth pathways, the most well known of which is the Jak2/STAT pathway.  In contrast, Prolanta (G129R) binds to one receptor but the arginine mutation blocks dimerization with a second receptor.  As a result, the intra-cellular profileration pathways are not initiated.  Prolanta binding also competitively blocks the binding of prolactin.  Additionally, our collaborators at MD Anderson Cancer Center have discovered that Prolanta can also initiate a cell death pathway, known as autophagy, initiated through PEA-15.  Not only does Prolanta block cell proliferation pathways, our drug also triggers autophagic cell death of tumor cells..........The aim of Oncolix's product development is to bring to market agents with increased efficacy and decreased toxicity in cancer therapy through targeted therapies. Prolanta is anticipated to be effective in the majority of ovarian and breast cancer patients as this therapy targets tumors that express the prolactin receptor which occurs in the majority of these tumors.