Oncolix Inc. (fka ONCX)

[WeeZuhl]

"Prolanta" (PRL-inh G129R) is a cool molecule with some intriguing biological effects in animal studies.

https://www.semanticscholar.org/paper/Blockade-of-the-Short-Form-of-Prolactin-Receptor-in-Wen-Wang/234101f684de2e88ca8469896a80a14fa87bafac/figure/2





The above graph shows the effect of Prolanta on proliferation of mouse uterine cancer cells.

Mannitol = Control group of uterine cancer cells
PRL = Add prolactin hormone to cancer cells
G129R = Add Prolanta drug to cancer cells
PRL/G129R = Add both prolactin hormone and Prolanta drug to cancer cells


Notice how prolactin hormone increases proliferation from baseline but Prolanta drug decreases proliferation from baseline. Also, on the far right, notice how the Prolanta drug fairly effectively cancels out the prolactin hormone when both are present. Like I said, Prolanta is a cool molecule with some intriguing biological effects in animal studies.




https://mct.aacrjournals.org/content/19/9/1943
(Firewall)

Cancer Biology and Translational Studies
Blockade of the Short Form of Prolactin Receptor Induces FOXO3a/EIF-4EBP1–Mediated Cell Death in Uterine Cancer

Mol Cancer Ther 2020;19:1943–54
Received November 6, 2019.
Revision received March 30, 2020.
Accepted July 7, 2020.
Published first July 31, 2020.

Abstract
Abnormal activity of human prolactin (PRL) and its membrane-associated receptor (PRLR) contributes to the progression of uterine carcinoma. However, the underlying mechanisms are not well understood, and current means of targeting the PRL/PRLR axis in uterine cancer are limited. Our integrated analyses using The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases demonstrated that a short form of PRLR (PRLR_SF) is the isoform predominantly expressed in human uterine cancers; expression of this PRLR_SF was elevated in uterine cancers in comparison with cancer-free uterine tissues. We hypothesized that the overexpression of PRLR_SF in uterine cancer cells contributes, in part, to the oncogenic activity of the PRL/PRLR axis. Next, we employed G129R, an antagonist of human PRL, to block the PRL/PRLR axis in both PTENwt and PTENmut orthotopic mouse models of uterine cancer. In comparison with control groups, treatment with G129R as monotherapy or in combination with paclitaxel resulted in a significant reduction of growth and progression of orthotopic uterine tumors. Results from protein profiling of uterine cancer cells and in vivo tumors revealed a set of new downstream targets for G129R. Our results showed that G129R induced sub-G0 population arrest, decreased nascent protein synthesis, and initiated FOXO3a/EIF-4EBP1–mediated cell death in both PTENwt and PTENmut uterine cancer cells. Collectively, our results show a unique pattern of PRLR_SF expression predominantly in uterine cancer. Moreover, FOXO3a and EIF-4EBP1 are important mediators of cell death following G129R treatment in uterine cancer models.