Lately, research on new anti-neoplastic drugs in the oncological field raises great hopes and expectations in more specific and less toxic therapies. In particular, last progresses in molecular biology are allowing studying both the different expression of genes engaged in neoplasia (genomic) and proteins produced by them (proteomic) in order to determine a detailed molecular profile of neoplasia. The following clinic-therapeutic application of these studies is capable (and will allow more in the next future) to personalize therapies on the tumor bimolecular featuring using selective drugs that act on its different targets by targeting the single changed molecules (growth factors, receptors, enzymes and so on) in charge of:
• growth and spread without control of tumor cells
• resistance to traditional therapies
• production of new blood vessels
These new remedies are often called: “target” or “biologic” or “intelligent”. They will allow, used alone, or in combination with traditional therapies (chemo-, radio-, ormonotherapy) to fight directly against tumor not involving the body normal cells with consequent minor toxicity.
The particular and advantageous features of these new remedies are:
1. selective action on particular substratum of tumor cells
2. not significant side effects also in the long lasting employment
3. possibility to be administered, in some cases, orally by keeping the patient in day hospital
4. possibility to be used in association with traditional therapies
On the other side these new target drugs have some limits in their use because of their field action limited to those tumor subgroups with specific molecular alterations.
Biological drugs are extremely selective in fact their aim is to hit precisely a single structure (receptor, protein and DNA sequence) in order to reduce side effects and increasing therapy effectiveness. They are the result of progresses achieved in biotechnologies field. Now there are some biological drugs available against some type of tumor and there are lots of studies made to increase their use in oncologic field where they represent a promise.
Biological remedies can interfere with Cytokines, which are some substances produced by immune system. Biological drugs forbid inflammatory Cytokines TNF-a, IL-1 and IL-6
In fact in the oncologic field last generation of biological drugs are getting extremely interesting results.
These new molecules influence the tumor growth, stopping the creation of some proteins that have a key role in this process. So they forbid cancerous cells development. Actually about fifteens of these remedies are actually used and more than thousands are those in testing clinic period.
The Herceptin has been the first used biological drug, it has been useful not only to reduce relapsing risk in operable breast cancer in more than 50% of cases, but it also caused an increase of survival in patients with breast cancer with EGFR receptor of type II (c-erbB2).
Lapatinib instead is one of the most recent and it’s effective in contrasting the appearance of breast cancer metastasis.
There are molecules used with positive results against colon tumor (cetuximab, used against EGFR receptor type I; bevacizumab used against a vascular growth factor VEGF) and some others (sunitinib, sorafenib) that opened new perspectives for the treatment of liver and kidney cancers, while until not long ago there were few therapeutically possibilities. In liver cancer the molecule called sorafenib had success in stopping the spread of this tumor and in surviving of patients under treatment.
Before there were not drugs able to modify the evolution of “liver cancer”, apart the local therapies (surgery, radiofrequency and embolism).Besides, recently have been announced results of a clinic study with the first oral biological remedy, erlotinib, that proved to enhance survival in patients with lung tumor in advanced phase, when today lung tumor is still the first cause of tumor death all over the world and, on average, in patients with metastasis it give a life expectation of about ten months.
It’s clear that Erlotinib lengthens significantly survival of patients with lung neoplasia and it helps in slowing down illness progression and in reducing also the coming out of painful symptoms such as cough and difficulties in breathing.
Thanks to this molecule life expectation is improved significantly and in patients who have peculiar biological features median survival is redoubled.
The taking of erlotinob at the end of the “classic” 4-6 cycles of chemotherapy significantly reduces the tumor progression risk satisfying patient request who would like that the maintenance therapy would respect his quality life.
In fact the simple taking of the pill allow the ill person to follow treatment at home: this would be impossible with traditional chemotherapy.
Researches on this molecule point out another interesting aspect: patients who better answer to the therapy are those with a particular genetic mutation, existing in 10% of ill people.
This is a further confirmation that genetic researches could give important information on pathologies features with encouraging treatment perspectives.
The mono-clonal antibodies are molecules able to stimulate immune system and to attack tumor cells without damaging normal cells significantly. The monoclonal antibodies have positive results also for the hematological neoplasia treatments; in particular Mabthera, in association with chemotherapy, significantly improve recovery probabilities in patients with some types of lymphoma no-Hodgkin.
Iressa it’s the first specific inhibitory of a protein “tyrosine kinas” associated to EGFR; this drug, administered orally in mono-therapy has showed an activity without precedent and a good tolerability in patients with lung tumor “with no small cells” previously treated with several chemotherapies lines.
Thanks to these data, the drug has been registered or it’s going to be registered in different countries for that patients’ group.
The association of Iressa with chemotherapy didn’t show any efficacious advantages with regards to patients treated only with chemotherapy.
Glivec it’s a specific protein inhibitory “tyrosine kinase” associated to c-kit receptor and it is a great revolution in oncology, putting together an extraordinary effectiveness with a very good tolerability.
Today Glivec, administered orally, it’s approved all over the world for the chronic myeloid leukemia and Gist, rare tumors of the gastrointestinal stroma.
For these type of tumors that belong to the sarcoma group and in generally comes out in stomach and intestine before Glivec the only therapeutically strategy was surgery.
This molecule changed significantly the Gist prognosis in advanced phase: in fact the 80-90% of cases has an important improvement not only in patient quality life but also in survival.
Actually thanks to these results this drug is studied also in the preliminary phase of the illness, after a surgery operation when benefits can be more evident.
Lonafarnib it’s an inhibitor of farnesol able to stop Ras oncogene, involved in the tumor growth in many neoplasia.
The evidence after test tube (in vitro) studies of a synergic action with chemotherapy raises the interest in research after disappointing initial results got with the employment of these agents in mono-therapy.
In fact on patients with tumor in advanced phase, such as lung tumors have been made several combination studies with preliminary interesting results.