AN EXCITING discovery highlighting a link between two prostate cancer treatments has provided the basis for a potential new therapy. In addition, this finding may have implications for other kinds of cancer.
Prostate cancer is the most common cancer in European males and the third most common cancer in Europe overall. Radiation and androgen ablation are two common forms of therapy used to treat the disease, and it is between these two treatments that researchers of the University of Virginia School of Medicine (UVA) found an unexpected link. The discovery has enabled a better understanding of how the therapies are connected at a molecular level, and may aid the development of new methods for treating prostate cancer. It is thought that this discovery will augment how doctors determine which forms of treatment will be most beneficial to individual patients.
The link, the checkpoint kinase (CHK)-2 pathway, is a cellular signalling pathway that halts cell division and facilitates DNA damage repair. Radiation therapy, which induces DNA damage, leads to the activation of this pathway. Another finding revealed that the CHK2 pathway also controls cell sensitivity to androgen, a hormone required by prostate cancer cells for growth. During androgen ablation, androgen is targeted and androgen receptor activity inhibited. Androgen and androgen sensitivity in turn affect prostate cancer cell susceptibility to radiation treatment, a discovery which may eventually make it easier to kill prostate cancer cells via manipulation of the CHK2 pathway; for example, blockade of the signalling process may sensitise cancer cells to radiation. The researchers also hypothesise that this signalling is lost with disease progression, which may explain why prostate cancer eventually becomes resistant to androgen deprivation therapy.
“The next steps are to see whether our predictions about…targeting this pathway could enhance cancer-killing in response to radiation or androgen ablation,” said Prof Dan Gioeli, Department of Microbiology, Immunology and Cancer Biology, UVA Cancer Center, Charlottesville, Virginia, USA. “Perhaps it would lead to a three-way combination where we would be looking at how androgen withdrawal sensitises tumour cells to radiation therapy and whether we can further enhance that sensitisation by inhibiting this pathway.”
Major pharmaceutical companies have already began to develop drugs that inhibit CHKs, and clinical trials using the products could potentially occur within 3–5 years.