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Rounding out the ‘genetic map’ of penile cancer which will enable more targeted therapies

Penile cancer represents about 17% of all tumors in males. A type of tumor that given its low prevalence can be labeled as “weird” and whose treatment is mainly based on surgery. In fact, with regard to aggressive tumors penis, that is, those just invade other organs – metastases  – therapeutic options are minimal.

Even today, patients have no targeted treatments for this cancer. Hence the importance of the evidence reached by researchers at the University of Michigan, which sets the first steps towards the development of treatment precision against penile cancer.

As Scott A. Tomlins, lead author of the study published in the journal “Cancer Research” explains, “taking into account the variability and genetic changes between primary tumors and metastases, it can be concluded that it is more difficult to establish targeted therapies for cancer of penis than for other types of cancer”.

However, it stresses Tomlins “penile cancer has similarities with other types of squamous cell carcinomas, such as lung tumors, head and neck or cervix, allowing us to design better studies to design more effective treatments against tumor “.

Most common mutations

To conduct the study, the authors analyzed 43 cases of squamous cell carcinoma of the penis in various stages of evolution and among others, identified a combination of common alterations in the ‘KRAS’, ‘HRAS’ and ‘NRAS’ as well as alterations in the gene “EGFR”. Importantly, because tumors with mutations in the ‘KRAS’ or ‘NRAS’ genes are resistant to treatment with receptor inhibitors, or epidermal growth factor EGFR, produced from the gene ‘EFGR’.

As Tomlins points, “for example, colon cancer is a low number of mutations in HRAS that has never been studied regarding possible resistance to EGFR inhibitors. However, based on the biology of HRAS, NRAS and KRAS, we can predict that the tumor will be resistant to these inhibitors. In the case of penile cancer, in which mutations in the gene ‘HRAS’ are relatively frequent, this alteration may condition the response to treatment with EGFR inhibitors”.

In addition, the study also shows differences between primary and metastatic lymph-level nodes in the pelvis tumors. A finding that shows that aggressive forms of the tumor as mutated start to spread, thus establishing the best treatment for studying various areas of the tumor is required. As alluded Tomlins, “it may not be as simple as administering a drug based on a single mutation detected in an area of the tumor. We need to know the total genomic profile from several tumor areas to establish the best therapeutic strategy”.

And to overcome this difficulty, researchers have developed a new genetic test that identifies the most common mutations in penile cancer. “We have the map to design better clinical trials in cancer of the penis. And we also have very good potential clues to therapeutic alternatives. And with all this, we have the basic knowledge needed to open the door to future individualized treatment”, concludes Dr. Tomlins.