Prostate cancer treatment can make tumor cells resistant to therapy

Prostate cancer treatment entails numerous considerations that must be contemplated carefully. An important paper just published in the prestigious journal Nature Medicine describes how prostate cancer treatment can change the tissue microenvironment in a way that makes the tumor cells more resistant to subsequent therapy. The authors state:

"Acquired resistance to anticancer treatments is a substantial barrier to reducing the morbidity and mortality that is attributable to malignant tumors. Components of tissue microenvironments are recognized to profoundly influence cellular phenotypes, including susceptibilities to toxic insults."

They investigated this phenomenon in prostate cancer by analyzing how the genes of prostate cancer cells responded to the stress of chemotherapy. They identified proteins secreted in the prostate cancer microenvironment in response to the genotoxic effects of treatment. These included the 'Wnt family member wingless-type MMTV integration site family member 16B (WNT16B)'...

"We determined that WNT16B expression is regulated by nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB) after DNA damage and subsequently signals in a paracrine manner to activate the canonical Wnt program in tumor cells. The expression of WNT16B in the prostate tumor microenvironment attenuated the effects of cytotoxic chemotherapy in vivo, promoting tumor cell survival and disease progression."

In other words, when the DNA in prostate cancer cells is damaged by chemotherapy, NF-κB activates the Wnt genes. This causes the tumor cells to be more 'hardy' and survive subsequent prostate cancer chemotherapy. This allows the disease to progress. Clinicians please note that NF-κB is a highly important target for benign pharma used for autoimmune disorders as well. The authors conclude:

"These results delineate a mechanism by which genotoxic therapies given in a cyclical manner can enhance subsequent treatment resistance through cell nonautonomous effects that are contributed by the tumor microenvironment."

Chemotherapy should never be the sole intervention in prostate cancer case management. A comprehensive treatment plan should take into consideration the multiple factors that influence the tumor micro and macro environments, cancer cell genetic expression, the hormonal and metabolic signaling that contributes to disease progression, and more.