Latest Treatment for Melanoma
Latest Treatment for Melanoma Researchers at the University of Pennsylvania’s Perelman School of Medicine have created a new therapeutic target for melanoma treatment. Years of research have linked female gender and previous pregnancy history to better outcomes with the diagnosis of melanoma. Now, a research team at the University of Pennsylvania School of Medicine says it can determine the cause of the protective effect against melanoma.
The mechanism involves a cellular protein called protein-bound estrogen receptor G (IPG). When IPG was activated and combined with PD-1 inhibitor anti-drugs in mouse cancer models, treatment survival was significantly prolonged in all animals and the tumor was completely removed in 50 percent of the mice. The researchers published their findings today in the Elife magazine.
Melanoma is the most lethal form of skin cancer, although it usually accounts for only one percent of skin cancers. Melanoma rates have been rising for 30 years, and the American Cancer Society estimates that there are more than 87,000 new cases in the United States in 2017. Even recent immunotherapies will die from most patients with metastatic melanoma forms.
“Melanomas and many other types of cancer have a better prognosis than men, and women with pregnancy stories seem to have a better prognosis than women who are not pregnant,” said Todd W. Ridky, senior editor of the study. , MD, PhD, a dermatology assistant professor at Penn. “Despite years of research, it definitely suggests that women sex hormones and something that helps protect your pregnancy against melanoma, but nobody really understands how it works.”
Researchers say that the key is IPG, a receptor found in melanocytes, and the cells that produce the pigment in it. The receptor is normally activated by estrogen, which is higher in women, especially during pregnancy. The activation of IPG explains why many women realize that many areas of skin in pregnancy are obscured. Previous Ridky Laboratory surveys have shown that the effects of IPG activation are completely different from the effects of classic estrogen receptor signaling, which is important in breast cancer. The team discovered that melanocytes do not even express the classical estrogen receptor, and that all estrogenic effects are the result of IPG.
Especially in melanoma, the cancerous cell is different after IPG is activated. It becomes less divided, more pigmented, and becomes more visible and vulnerable to the natural immune system. This makes it difficult for the cancer to become resistant to immunotherapy.
There are no drugs specifically targeted at IPG, but Ridky and his team used a laboratory compound called G-1, originally developed by Eric Prossnitz, PhD, at the University of New Mexico’s Comprehensive cancer Center to stimulate IPG in mice, And then he used anti-PD-1 inhibitors to treat melanoma. The approach eliminated the tumors in the middle of all the mice. The authors note that anti-PD-1 inhibitors, when used alone in mice with melanoma, extend survival modestly, but do not completely eliminate tumors, and no animal survives in the long term.
“We hope this work will inspire other researchers to revisit old ideas of differentiation-based cancer therapies now that immune therapies are available ” said study lead author Christopher A. Natale, a researcher In Ridky’s lab. “It is clear that the future of cancer therapy lies in combination therapies, and differentiation drivers can be a very useful component in future oncology therapy regimens. “
Latest Treatment for Melanoma
As Ridky designates, this represents a unique approach to immunotherapy and cancer therapy in general.
“Much of the cancer field is focused on inhibitors, but in this new treatment approach, we’re actually activating something instead of blocking it,” Ridky said. “We use a synthetic compound to mimic some of the things naturally occurring during pregnancy, and as a result, the IPG activator is very well tolerated, without the common toxic side effects of most cancer drugs.”
Ridky also said that this approach could be promising beyond melanoma.
“This is a receiver that is expressed in many organs, so there is a reasonable expectation that this can work in other types of tumors as well,” said Ridky.
Although the investigators did not observe any compound toxicity in mice, although they say they plan additional toxicity studies before we expect to move on to human trials.