Callerio Foundation

Linfa

LINFA why

LINFA originates from the experience cumulated in the course of studies on the most important pharmacological properties of a new ruthenium-based antimetastasis drug.

LINFA poses itself as a reference point for research on the antimetastasis properties of new complexes being identified within scientific institutions for basic research on the subject.

LINFA has the main goal of promoting studies on the pharmacological treatment by means of ruthenium-based drugs of metastases released by solid tumours.

INTRODUCTION

Cancer is the second cause of death in most western Countries. In the "developed" world cancer concerns one individual out of three within his/her lifespan and causes one death out of five. Although cardio-vascular diseases kill more people than cancer, and often at an earlier age, cancer is all the same the most awful plague of our time.

Nearly one half of all deceases due to tumours occurring in the developed world can be ascribed to stomach, lung, colon-rectum, breast and cervix cancers. These five tumours, together with those affecting the bladder, the oesophagus, the prostate and the skin, kill mainly because they produce metastases, and therefore when they are diagnosed they are already spread to a point that a a complete surgical removal is unfeasible. As a matter of fact, one of the main characteristics of malignant tumours is that some cells can get detached from the main mass and move freely around the body until they settle in some other tissue where they start the growth of a new tumour, the metastasis.

Metastases of solid tumours represent the main reason for the lack of success of anti-cancer therapies. Actually whereas surgery and/or radio-therapy may successfully treat the primitive tumour lesion, many human tumours develop remote metastases that, regardless for the diagnosis at the beginning of treatment, invariably lead patients to death. Because of their wide distribution, the pharmacological therapy seems to be the best choice for a successful treatment. Presently in this kind of approach the weak ring of the chain is represented by the available drugs.

These drugs are characterised by their capability of interacting with cell proliferation and growth mechanism by cytotoxicity, are poorly specific for tumour cells and their toxicity limits the dose to be used, often because of bone marrow impairment or of reduction of immune responses. It is remarkable that all presently available drugs were developed aiming at inhibiting tumour growth in its primary site rather than on systemic metastases. On the contrary, studies of the last twenty years have shown the peculiarities of solid tumour metastases with respect to the primary tumour from which they originated, with special reference to their different sensitivity to anti-tumour cytotoxic drugs.

Thus there is a particular attention and a strong demand for drugs featuring specific antimetastasis activity, as they represent - among the rest - also a solution to the tolerance problems that presently the chemotherapy poses to the neoplastic patient.


TARGET

The purpose of LINFA is to build up a national and international reference centre for the basic study of chemical structures among which new ruthenium-based antimetastasis drugs are to be identified.

LINFA is therefore a reference for several research laboratories where the synthesis-aimed research and the chemical characterisation of ruthenium complexes are carried on, among which:

The Department of Chemical Sciences, University of Trieste
(Prof. G. Mestroni)

The Department of Chemical Sciences, University di Florence
(Dr. L. Messori)

The Chemistry Institute, University of Leiden, Holland
(Prof. J. Reedijk)

The Department of Chemistry, University of Edinborough, Scotland
(Prof. P. Sadler)

The Instutute of Inorganic Chemistry, University of Vienna, Austria
(Prof. B. Keppler)

The Department of Chemistry, Royal College of Surgeons, Dublin, Ireland
(Prof. K. Nolan)

The Merkert Chemistry Center, University of Boston, USA
(Prof. M.J. Clarke)

The Department of Inorganic Chemistry, University of Sevilla, Spain
(Prof. F. Gonzales-Vilchez)

"Within laboratories for chemical synthesis are present new high-potentiality structures that cannot find enough opportunities of biological study for lack of adequate references for the pharmacological evaluation. Therefore LINFA proposes itself to these structures in order to allow and facilitate the study of anti-metastasis potentialities of new products, by using models aimed at studying the metastases of solid tumours."

Among LINFA 's goals there is also perfecting the pre-clinic study models concerning new metal-based drugs active on tumour metastases, by identifying those which best allow to simulate - within the ethical limits of the laboratory experimentation - the situation of human metastases-originated tumours.