Age-dependent Cancer Therapy: A Key Element in Treatment-resistant Melanoma

Age is a key factor in determining the efficiency of targeted therapy for Melanoma. Inhibition of BRAF oncogene is a targeted therapy approach to melanoma that is found to have less efficacy among older age.

Age is the primary factor in determining the efficacy of various types of cancer treatments for melanoma – unveil two studies at Johns Hopkins Kimmel Cancer Center and Johns Hopkins Bloomberg School of Public Health researchers, published in Cancer Discovery and in Clinical Cancer Research this year.

Melanoma is a deadly type of skin cancer affecting about 100,000 Americans annually. This cancer arises in melanocytes – cells responsible for imparting pigments to our skin. It is known to become more metastatic with advancing age.

Melanoma - Causes, Symptoms, Diagnosis, Treatment & Prevention
Melanoma of the skin is a dangerous type of skin cancer that usually appears as a cancerous mole due to exposure to the sun’s damaging UV rays.

‘Age is a key factor in determining the efficiency of targeted therapy for Melanoma. Inhibition of BRAF oncogene is a targeted therapy approach to melanoma that is found to have less efficacy among older age.’

The study incorporated dermal fibroblast (a common type of connective tissue required for wound healing) with melanoma cells, from aged and young animal models.

It demonstrated that aged fibroblasts increased the uptake & synthesis of fatty acids via the elevated number of fatty acid transporter FATP2, in melanoma cells and thereby showing resistance to targeted anti-cancer therapy as compared to young cells.

"Taking up a lot of fat protects melanoma cells during therapy", explains Weeraratna – senior author of the study. Earlier in 2016, the author had shown similar results where the targeted treatment against cancer-promoting BRAF oncogene had almost no response in aged mice as compared to young mice.

Promising New Tool may Fight Against Melanoma
Key cancer blood markers could be used to select the most effective treatment for melanoma, which can improve melanoma survival rates, reports a new study.

Upon depletion of FATP2, the response of melanoma cells to targeted therapy was dramatic even in aged mice models. Inhibiting FATP2 overcomes age-related resistance to BRAF/MEK inhibition in animal models, ablates tumor relapse, and significantly extends survival time in older animals – added the author.

Another study in Clinical Cancer Research included data from the AVAST-M trial of 1,343 patients with melanoma. They were subjected to analyze the age-dependent expression of angiogenesis-promoting gene VEGF and proangiogenic factor Secreted frizzled-related protein 2 (sFRP2) as well as response to anti-VEGF therapy – bevacizumab (Avastin).

Rapid Urine Test to Track Melanoma Progression
Current techniques of assessing melanoma progression in patients include invasive surgery to remove tissue samples. The samples then undergo expensive and time-consuming analysis. The invasive procedures often stop the patients from getting timely treatment.

Angiogenesis is a common process of forming new blood vessels for nourishment. It becomes detrimental when tumor cells signal the formation of new blood vessels for their further growth and metastasis. "Older patients have more angiogenesis, which helps cancer spread, but it is driven by sFRP2, not VEGF," says Fane, co-lead author of the study along with Brett Ecker and Amanpreet Kaur.

Hence the older patients showed poor response to anti-VEGF therapy – bevacizumab as compared to younger patients who had significant improvement to the therapy. But the efficacy was drastically overcome by increasing sFRP2 in young mice too, marking sFRP2 as an age-dependent targeted therapy for melanoma.

Innovative Smartphone-camera Adaptation Images Melanoma and Non-melanoma: Study
Standard smartphone technology can be adapted to screen skin lesions, providing a low-cost, accessible medical diagnostic tool for skin cancer, according to a new study.

Present studies demonstrated that older age (above 50 years) had a marked influence on cellular mechanisms responsible for the resistance to treatment, both in animal and laboratory models of melanoma cells. This stresses the importance of considering age as a factor for designing targeted therapies – concluded the author.

Source-Medindia