“The new era of intelligent drugs”: this was the title of the speech by Dr. Giovanna Masci, oncologist in Humanitas, during Mamazone 2017, the seventh edition of “Paziente diplomata”, a day dedicated to women with and without breast cancer, organized by Humanitas last 14 October.

“The use of the so-called intelligent drugs has been increasing for some years, but there are some that are so new that they have been used for a few months and others that will soon enter clinical practice. These drugs are true masterpieces of molecular engineering: they are synthetic products made in the laboratory with the aim of selectively hitting certain parts of the tumor cell, or the individual altered molecules responsible for the growth and uncontrolled spread of cancer cells (such as growth factors, receptors, enzymes). Because they are selective, these products are personalized and are taken orally, which is another advantage to take into account.

She then described the main intelligent medicines and what patients they are intended for.


The histological profile of the tumor

The histological profile of the tumor is the first step in understanding how this category of drugs can be used.

“From a biological point of view, there are three main breast cancers: tumors with positive hormonal receptors (about 60% of all breast cancers), tumors expressing the HER-2 protein (25%) and triple negative tumors (15%).

Receptors are proteins that are (or not) found on the cell membrane and to which the female estrogen and progestin hormones are bound. This process activates the tumor cell and promotes its duplication. Of the three types mentioned, only the triple negative does not express receptors: in fact it has neither the receptor protein for estrogen, nor that for progestin, nor for HER-2 (hence the name triple negative). This often includes mutated tumors, which are carriers of the mutation for BRCA1 and BRCA2,” said the specialist.


The role of drugs in tumor proliferation

“All of our tissues are made up of cells and each has its own functions. The tumor arises from the alteration of one of these cells, resulting in the onset of an uncontrolled growth process. This is the process that medicines are trying to counteract.

For example, in patients with estrogen- and progestogen-positive hormone receptors, drugs such as Palbociclib, Ribociclib and Abemaciclib block the activity of CDK 4- and CDK 6-dependent kinase-cycline enzymes, which are essential in regulating the way the cells grow and divide.

Palbociclib, at the moment is the only drug of the three that has entered clinical practice, the other two are expected shortly, and has opened interesting prospects for the treatment of metastatic breast cancer. In registration studies, the combination of Palbociclib with hormonal therapy (Letrozole or Fulvestrant) doubled survival without progression of disease. With these drugs we try to chronicise the cancer and postpone the use of chemotherapy.

For patients with hyper- expression of HER-2, however, Trastuzumab has been available for more than ten years: the drug binds to the HER-2 protein and blocks its growth, leading to the death of the tumor cell. From Trastuzumab we have switched to even more innovative drugs, such as Pertuzumab, which is directed against HER-2 but in a different place. Studies have shown that using Trastuzumab and Pertuzumab together (double block) allows for better therapeutic success. Another very active drug that has been in this patient setting for a few years is TDM-1.

Finally, there is Olaparib, which will soon be available for patients with triple negative tumor and BRCA1 and BRCA2 mutation.

The goal for the future is to find increasingly selective drugs with fewer and fewer side effects,” concluded Dr. Masci.


Watch the full interview with Dr. Masci, click here.