Targeted drugs are one of the great news of these years in the fight against tumors. But when cancer manages to develop the resistance to their action, even the most innovative therapies prove to be sprung up. This is the case of Pi3kα inhibitors, a very promising molecules for the treatment of head and neck cancers, but against which with time often neoplasia naturally develops a form of resistance. A new research of the National Institute of the Cancer Elena (IRe) and the Charité University Hospital of Berlin could soon change the situation. The study, published in the magazine Drug Resistance UpdateIn fact, it indicates a possible way to restore the action of Pi3kα inhibitors, and thus improve the effectiveness of care for many patients.
The tumors of the head and neck are rather common neoplasms, which in our country record about 10,000 new diagnoses every year, and which will be expected will become more and more common in the coming years. They are mainly male neoplasms, since they affect men in 70%of cases, and the most frequent locations are the oral cavity (42%), the pharynx (35%) and the larynx (24%). To date, these are poorly curable tumors, which have a high probability of recurrence and a low survival five years after the diagnosis.
Tumors of the head and neck
In many neoplasms of this group there is an alteration in the molecular signaling route that is based on the enzymes of the Pi3k family. A detail that makes the use of Pi3kα inhibitors particularly promising, drugs originally developed for the treatment of breast cancer that act specifically on the mechanisms that are changed in these neoplasms. Unfortunately, as we said their use in the therapy of head and neck cancers is complicated by the frequent appearance of forms of spontaneous resistance. For this reason, the researchers of the Regina Elena National Cancer Institute and the Charité University Hospital in Berlin have decided to study specifically the mechanisms with which cancer cells become resistant to the action of these drugs.
“Not always – explains Claudio Pulito, Ire researcher – tumors escape drugs because they change their genes: often, they regulate them differently. Understanding these mechanisms allows us to act with greater precision and develop smarter therapies”.
The study in fact identified a non -genetic resistance mechanism at Pi3kα inhibitors. The researchers observed that some microRNA, small molecules that regulate gene activity, deactivate a natural brake of cancer growth: the Pten protein. The resistance, therefore, would not depend on genetic mutations, but on an “alternative” mechanism that changes the regulation of genes without altering its DNA.
The new care
Once the Pten brake is deactivated, moreover, a second protein, PLK1, comes into play, which allows the tumor to find another way to survive. The good news is that there are already experimental molecules capable of blocking PLK1, which in laboratory models have reduced the vitality of resistant tumors. This opens the way to a possible combined therapy: by combining drugs against Pi3kα and Plk1 you could overcome the resistance and improve the effectiveness of the treatments.
“This type of research – concludes Konrad Klinghammer, of the Department of Medicine, Division of Oncology and Hematology, Charité – Universitätsmedizin Berlin – is essential to clarify the mechanisms at the basis of the disease and the resistance to treatments, and open the path to targeted development of innovative therapeutic strategies for patients with head and neck tumors”.