Introduction: Compounds blocking the prolactin receptor (PRLR) have not yet reached the clinic. There are however several observations supporting a future use of PRLR antagonist (PRLRA) for tumor treatments.Many drug have been used for cancer treatment and they are commenly associated with sever side effect, such a drug is Maytansine (DM1), a cytotoxic drug against cancer cells with neurotoxicity and multiple adverse effects on the gastrointestinal tract. Research pointed out the need for improved drugs that specifically deliver cancer drugs to the tumor aimed to be treated. Indeed, one has tested DM1 conjugated to a mono-clonal antibody to achive a tissue- specific-therapy. Aim: This study aimed to investigate the potential use the PRLR for drug delivery. A PRLR antagonist (PRLRA) and DM1 conjugated to PRLRA (PRLRA-ABD-DM)1 were tested on PRLR positive cancer cells. Methods: MCF7, U251, OV2008, OVSAHO and SKOV3 cell lines were screened for PRLR at mRNA and protein levels. MCF7 and U251 were selected and different read- outs were utilized: for PRL and PRLRA binding and internalization assay, phophorylation assay, effect on cell viability of PRLRA/PRLRA-ABD-DM1 using PRLR positive cancer cells. Results: MCF7 cells showed the highest levels of PRLR mRNA and PRLR protein followed by U251 cells. OVSAHO, SKOV3 and OV2008 showed low PRLR levels. We found that PRL and PRLRA binds to PRLR in the selected cells. Under the conditions used, we were not able to demonstrate clear effects of PRL on the viability of the selected cell lines. Treatment with PRLRA showed no effect on U251 cells but showed a significant effects at high doses in MCF7 cells. On the other hand, PRLRA-ABD- DM1 showed a significant decline in viability of both cell lines with IC50 of 82.9 nM and 70 nM for MCF7 and U251 respectively. Conclusion: Since the PRLRA-ABD-DM1 compound binds efficiently to the PRLR, it has the potential to provide a novel approach for anti-cancer treatment. Our work has defined cell systems and methods that are suitable to test for the bioactivity the PRLRA- ABD-DM1 compound. Although work remains to clearly demonstrate a PRLR dependent uptake of the DM1 conjugate, we have begun to optimize experimental systems to document if the PRLR is a suitable candidate to target and internalize cancer drugs.