CDK 4/6 Inhibitors – evolution of the paradigm
Roma, 20 novembre 2020
Responsabile Scientifico
Dott.ssa Ida Paris – Dirigente medico, Fondazione Policlinico Universitario A. Gemelli Roma, IRCCS
CDK4 and CDK6 are cyclin-dependent kinases that control the transition between the G1 and S phases of the cell cycle. The S phase is the period during which the cell synthesizes new DNA and prepares itself to divide during the process of mitosis. CDK4/6 activity is typically deregulated and overactive in cancer cells. There can be amplification or overexpression of the genes encoding cyclins or of the genes encoding the CDKs themselves. Additionally, loss of endogenous INK4 inhibitors, by gene deletion, mutation, or promoter hypermethylation, can also lead to overactivity of CDK4 and CDK6. A major target of CDK4 and CDK6 during cell-cycle progression is the retinoblastoma protein (Rb). When Rb is phosphorylated, its growth-suppressive properties are inactivated. Selective CDK4/6 inhibitors “turn off” these kinases and dephosphorylate Rb, resulting in a block of cell-cycle progression in mid-G1. This causes cell-cycle arrest and prevents the proliferation of cancer cells. Although the initial response to a selective CDK4/6 inhibitor is typically cell-cycle arrest, in some cases arrested cells enter a state of senescence. Understanding the determinants of whether a cell undergoes reversible G1 arrest or enters a senescent state is an important research area. Cancer cells entering senescence may undergo gradual regression over time; it is in such cancers that CDK4/6 inhibitors may produce the greatest clinical benefit. This mechanism of action is known in estrogen receptor– positive breast cancer and seems to be dependent upon CDK4 for proliferation. To date, estrogen receptor–positive breast cancer is the malignancy for which this class of drugs has proven most effective and for which we have the most mature data from randomized trials comparing these drugs with endocrine therapy alone. Besides abemaciclib demonstrated an important activity in endocrine-resistant patients thus determining a survival prolongation delaying the time to chemotherapy. These results had never been seen in these setting of patients.
This meeting would like to review the mechanisms of action and efficacy of these drugs in order to evidence the best choice in clinical management of estrogen receptor–positive metastatic breast cancer with special point of view in their future development.
L’evento è accreditato ECM per 50 Medici Chirurgo (specializzazioni: anatomopatologi, ginecologi, oncologi, senologi, radioterapisti) e Infermieri.
ASTONE Antonio
Fondazione Policlinico Universitario A. Gemelli, Roma
BOTTICELLI Andrea
Ospedale Sant’Andrea Roma
BRIA Emilio
Fondazione Policlinico Universitario A. Gemelli, Roma
CANNITA KATIA
Dirigente Medico I livello, U.O Oncologia Medica, Presidio Ospedaliero S.Salvatore – L’Aquila
CORSI Domenico
Direttore U.O.C di Oncologia S. Giovanni Calibita Fatebenefratelli Roma
DANESI Romano
Azienda Ospedaliero Universitaria Pisana
D’AURIA GIULIANA
Dirigente medico presso San Filippo Neri Roma
DE ANGELIS Carmine
Azienda Ospedaliera Universitaria Federico II, Napoli
D’ONOFRIO Loretta
Campus Bio Medico Roma
FABBRI Agnese
Ospedale Belcolle, Viterbo
FABI Alessandra
Istituto Tumori regina Elena Roma
FEBBRARO Antonio
Ospedale Fatebenefratelli Benevento
GAMUCCI Teresa
Ospedale Sandro Pertini, Roma
GENERALI Daniele
Professore Associato Oncologia Medica Università di Trieste
MASETTI Riccardo
Università Cattolica del Sacro Cuore, Roma
MINELLI Mauro
Azienda Ospedaliera San Giovanni Addolorata, Roma
PARIS Ida
Fondazione Policlinico Universitario A. Gemelli, Roma
ORLANDO Laura
Ospedale Perrino Brindisi
PORTARENA Ilaria
Policlinico Tor Vergata, Roma
SALESI Nello
Asl di Latina
SCAMBIA Giovanni
Università Cattolica del Sacro Cuore
VICI patrizia
UOC Oncologia Medica 2, Istituto Regina Elena, Roma
VIGNERI Paolo
Professore Associato Oncologia Medica Università di Catania Dip Medicina Clinica e sperimentale
KRASNIQI Eriseld
Medico oncologo e collaboratore di ricerca presso ISTITUTO NAZIONALE DEI TUMORI REGINA ELENA – IRCCS (IFO)
Programma
h. 9.00 – Saluto delle autorità e presentazione del corso. Prof Scambia – Prof Masetti
Lezione magistrale – Prof. Emilio Bria
h. 9.15 – Metodologia clinica applicata agli studi con inibitori delle kinasi ciclino-dipendenti
SESSIONE 1 – Moderatori: Dr.ssa Teresa Gamucci, Dr.ssa Patrizia Vici, Dr. Antonio Astone
h. 10.00 – Trattamento della patologia mammaria luminale endocrino-sensibile
Dr. Carmine De Angelis
h. 10.30 – Trattamento della patologia mammaria luminale endocrino-resistente
Prof. Daniele Generali
h. 11.00 – Coffee Break
SESSIONE 2 – Moderatori: Prof. Paolo Vigneri, Dr.ssa Alessandra Fabi, Dr. Domenico Corsi
h. 11.30 – Interazioni farmacologiche e polimorfismi genetici
Prof Romano Danesi
h. 12.00 – Management della tossicità da CDK4/6
Dr.ssa Loretta D’Onofrio
h. 12.30 – Recenti acquisizioni in tema di CDK4/6 inhibitors e prospettive future
Dr.ssa Ida Paris
h. 13.15 – Light Lunch
Sessione 3 – Clinical cases; Moderatore: Dr Mauro Minelli
h. 14.15 – Clinical case 1: Dr Antonio Febbraro
Pros & Cons: Dr Eriseld Krasniqi, Dr Nello Salesi
h. 14.45 – Clinical case 2: Dr.ssa Laura Orlando
Pros & Cons: Dr.ssa Ilaria Portarena, Dr Andrea Botticelli
h. 15.15 Clinical case 3: Drssa Katia Cannita
Pros & Cons: Dr.ssa Agnese Fabbri, Dr.ssa Giuliana D’Auria
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