In a new study led by researchers at the University of Michigan Comprehensive Cancer Center, it has been identified that potential genetic alterations in penile cancer that could pave the way for targeted treatments.
Penile cancer is characterized by malignant growth on the skin or in the tissues of the penis. Around 95% of penile cancers can be categorized as squamous cell carcinomas. This type of cancer represents about 17 percent of all cancers in men. While a rare disease, the study also dwelled on some of the key similarities with other squamous cell cancers, like lung cancer, head and neck cancer, and cervical cancer. The details of the study were published in Cancer Research recently.
For many patients suffering from this rare form of cancer, surgery is the only option. But in aggressive forms of penile cancer, few therapeutic options exist, targeted therapies in particular. The new study describes a complex landscape that could suggest potential clinical trials of targeted therapies and potential limitations in some patients.
Scott A. Tomlins, M.D., Ph.D., assistant professor of pathology and urology at the University Of Michigan Medical School and a senior author of the study said it is observed that determining the best targeted therapies may be more complicated in penile cancer than in other cancers based on the combinations of genetic changes and variability between primary tumor and metastases.
As a part of the study, next generation sequencing was performed by the researchers on 43 cases of penile squamous cell carcinoma. The cases were of various types differing in stage, grade and subtype. Fourteen samples were matched to include the primary tumor and metastatic tissue. It was found by the researchers that there is a common combination of alterations in the genes KRAS, HRAS and NRAS, as well as alterations in the gene EGFR. Tumors like colon cancer are commonly treated with EGFR inhibitors, while tumors with KRAS or NRAS mutations are resistant to EGFR inhibitors. Importantly, clinical trials are planned using EGFR inhibitors in penile cancers based on anecdotal examples of clinical response.
Sequencing done on the sample used in the study was done using the Oncomine Comprehensive Panel, a new assay that assesses the most common genetic variants across cancer types. The assay is being used in the National Cancer Institute MATCH trial and was developed and validated by researchers at the University of Michigan and Thermo Fisher Scientific.
Tomlins remarked that in colon cancer, there are so few HRAS mutations that their resistance to EGFR inhibitors hasn't been tested. But based on the biology of HRAS, NRAS and KRAS, it is safe to predict that they do cause resistance. As HRAS mutations are relatively common in penile cancer, this alteration may impact the tumor’s response to an EGFR inhibitor in this cancer type.
Also, the researchers found differences between the original primary tumor and metastases in the pelvic lymph nodes. In most cancers, the best therapeutic targets are the same in primary tumors and metastases, which suggests that genetic changes occur early in cancer’s development. As per these findings, aggressive forms of penile cancer mutate as they spread. So, more than one area of tumor may need to be studied to identify the best therapeutic target for a given patient. That means that matching one drug with one mutation based on a single sample in penile cancer is not sufficient. Tomlins remarked that it may be needed to take the genomic profile in total from one or more areas to determine best strategies.
Tomlins remarked that it provides a roadmap to design better, more informed trials for penile cancer. Thanks to this study, now there are some good leads for potential therapeutic and individualized approaches.