Cancer at the time of "biomarkers" So you hit the right target

Some time ago, Leonard Saltz, a well-known American oncologist working at the Memorial Sloan Kettering Cancer Center in New York City, received a letter from a person who, during a television program on promises of "precision oncology", had listened The patient testifies how, after taking some pills, his tumor was gone. Even his father, sick, could hope for such a targeted and effective therapy, asked the author of the letter? Saltz comments in an editorial, just published in the scientific journal Nature : "Here's what people think about" precision oncology "and, damn it, I hope that It's really like that. " But for now, this is not the case: the possibility of "hitting the tumor in the heart" with the right drug based on its biological characteristics and, especially, genetic, detected by a test, is still limited. And the expectations of the public are a little exaggerated compared to the current clinical reality.

Biomarkers and other factors

It is not by chance that the editorial of Nature comes after the Asco, the meeting of the American Society of Clinical Oncology, held in Chicago. Meeting that had precisely the theme of precision medicine and the opportunities offered by the new tests. Let's start with the commentary of Nature to understand, today, if and how it is implemented in our country, this new medicine and what are the different biomarkers evaluable by old and new tests ( for biomarkers are meant or proteins produced from the tumor or particular genetic defects present in the tumor cell or genetic material of the tumor detectable in the blood) that can 'guide the clinician's hand' in the choice of the most appropriate for each patient. With a premise. "An oncologist – says Pierfranco Conte, professor of oncology at the University of Padova and director of the division of oncology at the Venetian Institute of Oncology – should not count only on the biomarkers to prescribe a therapy.It must take into account other factors such as the clinical condition of the patient, his clinical history, his ability to accept treatment. "

The person as a whole

Precision Medicine, in fact, does not only refer to drugs: it means taking into consideration the person as a whole, including his psychological characteristics, his lifestyle habits and the environment he lives, as the Reminded Asco President Bruce Johnson in Chicago.Not by chance there are also those who call it "personalized medicine." Of course, then one must choose the therapy capable of Attacking "this" single tumor: here, to help the cli nician, the lab arrives. We are entering the complex world of biomarkers. "Which are of two types – continues Conte -. Tissue cells, present in tumor cells (usually those on the surface or alterations of cellular DNA, ndr ) or those which, on the contrary, can be detected in the blood (or in other body fluids: generally they are fragments of genetic material of the tumor, ndr ). Some of these biomarkers have long been in clinical practice, others are coming or are still in the experimental phase. "Two" clbadic "biomarkers are bad cancer and are: hormone receptors and Her2 receptors.

Target Molecular Therapies

" These are both prognostic and predictive biomarkers of treatment response – more Conte -. Patients with positive hormone receptors are better (here is the prognosis, ndr ) and respond better to hormone therapy (here is the predictivity, ndr ). Her2-positive tumors are more aggressive, but are sensitive to treatment with an anti-Her2 drug, trastuzumab. We are talking here about targeted molecular therapies, the so-called targeted therapies . And if neither of the two markers is present? The solution in this situation is chemotherapy: even here, to choose on a case by case basis. Then there are the genetic markers identified by tests on tumor tissue, already entered into clinical practice, and those on the blood: we are talking here about the "liquid biopsy" that is starting to make its way, because it is easier compared to that of conventional fabrics. At the present time, this test may be useful for monitoring therapy in those who already have a tumor. Its use in early diagnosis still needs to be discussed, although it is promising.

Genetic alterations of tumors

Question. Which tumors have identifiable genetic alterations that are useful in current clinical practice? "At the moment, there are four or five tumors that can present genetic alterations" that can be attacked "by therapies – explains Giuseppe Curigliano, head of new drug development at the European Institute of Oncology at Milan – These are tumors of the colon (the alteration is called K-Raf or B-Raf), including the Gist (ie gastrointestinal stromal tumors affecting the connective tissue. , where the alteration is called C-Kit, ndr ), some lung tumors (altered genes are Alk, Egfr, Ros-1, Met), ovarian neoplasms (where the presence of mutated gene Brca1 account) ". The acronyms are difficult, but for each of these mutations, there are molecular targets, able to touch them, which in some cases are almost "miraculous" to increase the survival of these patients and even succeed in becoming chronic. Immunotherapy has been added to these treatments in recent years. Immunotherapy involves stimulating the immune system to fight the tumor by "unblocking" lymphocytes (specific white blood cells) capable of attacking tumor cells "frozen" by the tumor itself. How? Acting mainly on some of their receptors, the so-called Pd1. "The more these Pd1 receptors are expressed on lymphocytes, the more the drugs directed against them work," says Curigliano.

How Immune Therapy

"These are drugs that act in" black and white "- adds Conte -. Either they work well or they do not work properly. Unlike chemotherapy, hormone therapy or molecular targets, which work with different 'shades of gray' ". But, when immunotherapy works, it can guarantee a ten-year survival even to a patient with melanoma, a tumor that was a poor prognosis a few years ago. And that's just one example. The use of immunotherapies extends to many forms of cancer (including lung cancer) and the effort now is to understand which patients can respond to these therapies (because they work more or less in 20% of cases). The "measurement" test of the quantity of Pd1 receptors is already available and reimbursed in Italy. But a new test is underway, called Tumor Mutational Burden (Tmb), which measures the amount of mutations in the tumor's DNA (for the moment non-refundable). "Indeed, we know that the more the tumor has changed, the more it will respond to immunotherapy" concludes Conte

What are the tumors to be sequenced?

Is it really worth going to the spasmodic search for genetic alterations of the tumor to personalize the therapy? If you ask for an editorial appeared in the newspaper Nature . It is true that at least thirty anti-cancer drugs available today work if there is a specific genetic alteration in the tumor. And many patients benefit, but many, then, have relapses. So the questions: which tumors should be sequenced? And when? And what should we look for? Mutations of 50 genes, of 400 or is it better to study the entire genome of cancer cells? Questions in search of answers, also considering the high cost of these investigations. The hope of being able to cure tumors is always more important, says the editorial of Nature but one should not indulge in easy optimism by believing in the oncology of the precision.

The patient and the mouse -avatar

An avatar for each cancer patient, it is an alter ego that, in parallel, suffers from the same disease. And this may suggest how the tumor progresses, what are the mutations in the DNA that appear over time (and that can make the treatment ineffective) and which other drugs, gradually, can be chosen to control the disease. The avatar, at present, is a mouse where you can transplant the cancer cells of a patient and see how they behave in the laboratory. Science fiction? Not really. Because Giuseppe Curigliano, at the European Institute of Oncology of Milan, does it. We always talk about experimentation and not about something that is within everyone's reach. "We are working on it – ensures the expert -. In fact, tumors evolve over time. It would be important to identify the genetic mutations that present themselves gradually and to "choose" among available drugs those that can counteract these mutations. "Cancer research has recently changed course: the idea of ​​treating cancer no longer rests on the affected organ, but on its genetic identity card.In some cases, there is no longer talk of a lung cancer drug, but one of drug, directed against a certain genetic mutation that may be present in lung cancer, but also, for example, in one of the liver or liver, ovarian cancers.Therefore, the drug in question could also to be used in these cases