Prostate Cancer

Prostate cancer remains a significant public health concern, as it is the most common cancer and the second leading cause of cancer-related deaths among men in the United States. At Alfa Cytology, our team of renowned experts has been at the forefront of exploring the therapeutic potential of poly(ADP-ribose) polymerase (PARP) inhibitors for prostate cancer therapy.

PARP as a Therapeutic Target for Prostate Cancer

PARP is essential for repairing single-strand breaks in DNA. By facilitating the repair process, PARP helps maintain genomic integrity in cells, including cancer cells. In metastatic prostate cancer (mCRPC), germline or somatic mutations in DNA repair genes occur in approximately 20-30% of patients. Key genes involved include:

BRCA1/BRCA2: Well-known for their role in homologous recombination repair.

ATM: Involved in sensing DNA damage and signaling for repair.

FANCA, CHEK2, PALB2, CDK12, RAD51D: Other important genes that contribute to DNA repair mechanisms.

Fig. 1 PARP inhibitors in gastric cancer. (Wang Y., et al. 2021) Fig. 1 PARP inhibitors in prostate cancer. (Mollica V., et al. 2021)

In cancer cells with mutations in DNA repair genes, inhibiting PARP leads to the accumulation of DNA damage that cannot be repaired, resulting in cell death. This allows for targeted killing of cancer cells while sparing normal cells with intact DNA repair pathways. Therefore, PARP inhibitors have emerged as compelling targeted therapies for prostate cancer.

PARP Inhibitor Development for Prostate Cancer

Over the past decade, the development of PARP inhibitors has been a significant focus in the field of prostate cancer research and treatment. Several landmark clinical trials have demonstrated the efficacy of these targeted agents in the management of mCRPC. Clinical trials of PARPi in mCRPC are ongoing and include the following:

PARP Inhibitor	Combination Therapy	NCT	Phase
Niraparib	AR signaling inhibitors, Abiraterone Acetate	NCT03748641
Olaparib	immune checkpoint inhibitors, Durvalumab	NCT03810105
Olaparib	immune checkpoint inhibitors, Pembrolizumab	NCT02861573
Pamiparib	PARPi chemotherapy agents, Temozolomide	NCT03150810

Our Services

At Alfa Cytology, our multifaceted expertise in PARP biology, drug development, and biomarker discovery positions them as a valuable partner in accelerating the advancement of novel PARP inhibitor-based therapies for prostate cancers.

Small Molecule Inhibitors Development

Optimizing potency, selectivity, and pharmacokinetic properties of small molecule PARP inhibitors.
Exploring novel structural scaffolds and mechanisms of PARP inhibition.

Peptide Inhibitor Development

Developing cell-penetrant, stable, and potent PARP-binding peptides
Novel peptide engineering techniques like cyclization, stapling, and site-specific modifications can enhance the drug-like properties of PARP-targeted peptides.

Our Prostate Cancer Modeling Services

In Vitro Models

Standard, genetically modified, and patient-derived cell lines.
3D models such as spheroid and organoid cultures.
Scaffold and hydrogel cultures.
Tissue slice models.

In Vivo Models

Tumor xenograft models.
Patient-derived xenograft (PDX) models.
Circulating tumor cell (CTC) explant models.
Transgenic and genetically engineered mouse models.

At Alfa Cytology, we are committed to advancing the field of prostate cancer treatment through the development of cutting-edge PARP inhibitor therapies. If you are interested in exploring our services or collaborating on PARP inhibitor research, please don't hesitate to contact us. We are eager to discuss how we can support your research efforts and contribute to the ongoing progress in prostate cancer care.

Reference

Mollica V., Marchetti A., and et al. An Insight on Novel Molecular Pathways in Metastatic Prostate Cancer: A Focus on DDR, MSI and AKT. Int J Mol Sci. 2021, 22(24): 13519.

For research use only. Not intended for any clinical use.