Povezivanje mehanizama kemorezistentnosti tumorskih stanica i suboptimalnih sistemskih citotoksičnih rezultata liječenja

Systemic cytotoxic chemotherapeutic treatment of malignant tumors does not fully meet its goal due to the resistance of present tumor cells to the applied therapy. Chemoresistance is complex and multifactorial, caused by numerous mechanisms that alter drug concentration in the cell, by changes in expression of the epidermal growth factor and by activation of intracellular signaling pathways PI3K / Akt and MAPK. The factor of chemoresistance is also an increased level of antioxidative glutathione and glutathione transferase – S enzyme and the presence of tumor stem cells that signifi cantly improve protection of DNA from damage. Apart from cellular factors, resistance is influenced by extracellular hypoxia and acidosisand autophagy. Overcoming the chemoresistance is possible by using nanomechanisms for delivery of drugs to tumor cells, autophagy inhibitors like antimalarials chloroquine and hydroxychloroquine and plant polyphenols. By better understanding the mechanisms of chemoresistance and it’s overcoming it can be possible to achieve improvement in antitumor treatment.Sustavno citotoksično kemoterapijsko liječenje zloćudnih tumora ne ispunjava u potpunosti svoj cilj zbog prisutne kemorezistencije tumorskih stanica na primjenjenu terapiju. Kemorezistencija je kompleksna i uzrokovana brojnim mehanizmima koji mijenjaju koncentraciju lijeka u stanici, promjenama u ekspresiji epidermalnog čimenika rasta i aktivacije unutarstaničnih signalnih puteva PI3K/Akt i MAPK. Čimbenik kemorezistencije je porast antioksidativnog enzima glutationa i glutation-S transferaze te prisustvo matičnih stanica karcinoma koje značajno bolje štite DNA od oštećenja. Osim staničnih čimbenika, na rezistenciju utječe ekstracelularna hipoksija i acidoza te autofagija. Prevladavanje kemorezistencije moguće je primjenom nanomehanizama u dostavi lijekova u tumorske stanice, inhibitorima autofagije antimalaricima klorokinom i hidroksiklorokinom te biljnim polifenolima. Poznavanjem mehanizama kemorezistencije i njezinim nadilaženjem moguće je poboljšati dobrobit antitumorskog liječenja

Taksani u liječenju ranog raka dojke

Taxanes are irreplaceble drugs in treatment of many solid malignancies. In breast cancer they represent the backbone of adjuvant therapy and are important option in treatment of advanced and metastatic disease. Since their discovery in 1960’s they went through a long journey of clinical development and positioning in clinical practise of treatment of early breast cancer. Taxanes belong to the fourth group of cytotoxic drugs, which act as mytotic inhibitors, causing the death of the cell in metaphase. Clinical trials conducted in patients with breast cancer evaluated different combinations of other chemotherapeutics with taxanes, different modes of administration, effectiveness of different chemotherapy regimens including taxanes in different subtypes and stages of the disease and effectiveness of individual taxanes in comparison with one another. Based on the results of those trials, today the relevant global oncology associations reccomend the use of taxanes in treatment of early breast cancer, pointing out their significant benefit in total reduction of breast cancer mortality and risk of disease reccurence by 20-30% comparing to anthracycline only protocols. The purpose of this literature review was to provide comprehensive information about development of taxanes and their position in routine everyday clinical practise.Taksani su nezamjenjivi lijekovi u liječenju mnogih solidnih tumora. U karcinomu dojke predstavljaju okosnicu adjuvantne terapije i važna su opcija u liječenju uznapredovale i metastatske bolesti. Od njihovog otkrića 1960-ih prošli su dugi put kliničkog razvoja i pozicioniranja u kliničkoj praksi liječenja ranog raka dojke. Taksani pripadaju četvrtoj skupini citotoksičnih lijekova koji djeluju kao inhibitori mitoze, koji uzrokuju smrt stanice u metafazi. Klinička istraživanja provedena na bolesnicama s karcinomom dojke procjenjivala su različite kombinacije drugih kemoterapeutika s taksanima, različite načine primjene, djelotvornost različitih kemoterapijskih protokola koji uključuju taksane u različitim podtipovima i stadijima bolesti te učinkovitosti pojedinih taksana u usporedbi s drugim. Na temelju rezultata tih pokusa, danas relevantne globalne onkološke udruge preporučuju uporabu taksana u liječenju ranog raka dojke, pokazujući njihovu značajnu korist u ukupnom smanjenju rizika od smrti i povrata bolesti za 20-30% u odnosu na protokole bazirane samo na antraciklinu. Svrha ovog pregleda literature je pružanje sveobuhvatne informacije o razvoju taksana i njihove pozicije u rutinskoj svakodnevnoj kliničkoj praksi

Očuvanje plodnosti u mladih žena s ranim rakom dojke

Although breast cancer (BC) occurs more often in older women, it is the most commonly diagnosed malignancy in women of childbearing age. Owing to the overall advancement of modern medicine and the growing global trend of delaying childbirth until later age, we find ever more younger women diagnosed and treated for BC who have not yet completed their family. Therefore, fertility preservation has emerged as a very important quality of life issue for young BC survivors. This paper reviews currently available options for fertility preservation in young women with earlystage BC and highlights the importance of a multidisciplinary approach to fertility preservation as a very important quality of life issue for young BC survivors. Pregnancy after BC treatment is considered not to be associated with an increased risk of BC recurrence; therefore, it should not be discouraged for those women who want to achieve pregnancy after oncologic treatment. Currently, it is recommended to delay pregnancy for at least 2 years after BC diagnosis, when the risk of recurrence is highest. However, BC patients of reproductive age should be informed about the potential negative effects of oncologic therapy on fertility, as well as on the fertility preservation options available, and if interested in fertility preservation, they should be promptly referred to a reproductive specialist. Early referral to a reproductive specialist is an important factor that increases the likelihood of successful fertility preservation. Embryo and mature oocyte cryopreservation are currently the only established fertility preservation methods but they require ovarian stimulation (OS), which delays initiation of chemotherapy for at least 2 weeks. Controlled OS does not seem to increase the risk of BC recurrence. Other fertility preservation methods (ovarian tissue cryopreservation, cryopreservation of immature oocytes and ovarian suppression with gonadotropin-releasing hormone agonists) do not require OS but are still considered to be experimental techniques for fertility preservation.Premda se karcinom dojke češće javlja u starijoj životnoj dobi, to je i najučestaliji malignitet u žena reproduktivne dobi. Zbog sveukupnog napretka moderne medicine i rastućeg globalnog trenda odgađanja rađanja djece za kasniju dob suočavamo se sa sve više mladih žena s dijagnosticiranim i liječenim karcinomom dojke koje još nisu kompletirale obitelj. Stoga je područje očuvanja plodnosti postalo jako bitno u očuvanju kvalitete života mladih žena koje su preboljele karcinom dojke. Ovaj rad iznosi trenutno dostupne metode za očuvanje plodnosti u mladih žena s ranim karcinomom dojke i ističe važnost multidisciplinarnog pristupa u očuvanju plodnosti kao bitnog čimbenika kvalitete života tih žena. Smatra se da trudnoća nakon karcinoma dojke nije povezana s povišenim rizikom od recidiva pa stoga ne treba obeshrabriti žene koje žele ostvariti trudnoću nakon provedenog onkološkog liječenja. Danas se preporuča pričekati s trudnoćom barem 2 godine nakon postavljene dijagnoze za vrijeme kada je rizik od povrata bolesti najveći. No, isto tako bi bolesnice reproduktivne dobi trebalo obavijestiti o mogućem negativnom učinku onkološke terapije na plodnost te o dostupnim metodama očuvanja plodnosti i u slučaju zainteresiranosti za očuvanje plodnosti bolesnice treba žurno uputiti reproduktivnom specijalistu. Rano upućivanje reproduktivnom specijalistu je bitan čimbenik koji povećava izglede za uspješno očuvanje plodnosti. Krioprezervacija embrija i zrelih oocita su trenutno jedine standardne metode očuvanja plodnosti koje zahtijevaju stimulaciju ovarija kojom se odgađa početak kemoterapijskog liječenja barem 2 tjedna. Smatra se da kontrolirana stimulacija ovarija ne povećava rizik od povrata karcinoma dojke. Druge metode očuvanja plodnosti (krioprezervacija tkiva jajnika, krioprezervacija nezrelih oocita, ovarijska supresija GnRH agonistima) ne zahtijevaju primjenu ovarijske stimulacije, ali se i dalje smatraju eksperimentalnim metodama za očuvanje plodnosti

Point prevalence of significant nutritional risk among cancer patients in Croatia – research study of the Section of young oncologists, Croatian society for medical oncology of Croatian medical association

Cilj istraživanja: Utvrditi trenutačnu prevalenciju znatnoga nutritivnog rizika među onkološkim bolesnicima u Republici Hrvatskoj. Ispitanici i metode: Ova presječna studija ugniježđena je u prospektivnu kohortnu studiju Sekcije mladih onkologa HDIO-a HLZ-a, koja je provedena u Hrvatskoj tijekom 2017. godine na susljednom uzorku onkoloških bolesnika biranome prema redoslijedu dolaska na liječenje. Nutritivni probir proveli smo uporabom upitnika za procjenu nutritivnog rizika NRS-2002. Prema njemu, bolesnik se smatra nutritivno ugroženim ako je rezultat ≥ 3. Rezultati: U istraživanje je uključeno 275 bolesnika, medijana (interkvartilnog raspona) dobi od 61 godine (51 – 68), među kojima je bila 161 žena (58,5%). Bolesnici su liječeni u jedanaest onkoloških centara u Hrvatskoj. U 60 bolesnika (21,8%; 95%-tni CI 17,1 – 27,2%) utvrđen je znatan nutritivni rizik (NRS-2002 ≥ 3) koji indicira potrebu za nutritivnom intervencijom. Bilo kakvu nepovoljnu promjenu tijekom 30 dana prije uključivanja, dakle, gubitak tjelesne mase ili smanjen unos hrane, primijetilo je 127 (46,2%) sudionika. Zaključak: Naše istraživanje potvrdilo je da znatan broj onkoloških bolesnika u Hrvatskoj ima neki stupanj nutritivnog rizika te da je u više od četvrtine potrebna nutritivna intervencija. Nutritivni probir prvi je korak u dugoročnoj kontroli komplikacija vezanih uz promijenjen unos hrane i nutritivni rizik, kao i pri poboljšanju kvalitete života onkoloških bolesnika te prognoze ishoda bolesti pa bi ga, s obzirom na prikazane rezultate, trebalo rutinski provoditi.Objective of the Study: To determine the point prevalence of significant nutritional risk among cancer patients in Croatia. Subjects and Methods: This cross-sectional study was nested in the prospective cohort study of the Section of Young Oncologists of the Croatian Society for Medical Oncology, Croatian Medical Association, conducted in Croatia during 2017 on the consecutive sample of cancer patients selected by the order of their arrival to the exam.Nutritional screening was performed using the NRS-2002, According to NRS-2002, the patient is considered to be at significant nutritional risk if the result is ≥3. Results: We included 275 patients treated at eleven cancer centers in Croatia. In 60 patients (21.8%, 95% CI 17.1% -27.2%) we identified the significant nutritional risk (NRS-2002 ≥3) what indicates the need for the nutritional intervention. Any change during 30 days prior to screening, such as loss of body weight or reduced intake of food, was expressed by 127 (46.2%) participants. Conclusion: Our study has confirmed that a significant number of cancer patients in Croatia are in some degree at nutritional risk, and that more than one quarter need nutritional intervention. Nutritional screen poing is the first step in the long-term control of complications associated with altered food intake and nutritional risk, as well as in improving the overall quality of life of cancer patients and the prognosis of disease outcomes, so regarding the presented results, it should be routinely implemented