Imunoterapija karcinoma prostate

Prostate cancer is one of the most commonly diagnosed cancers in men and also one of the leading causes of their cancer-related deaths. Despite recent advances in the treatment of metastatic castration resistant prostate cancer, agents providing durable disease control and long-term survival are still needed. Therefore, various anti-cancer immunotherapy approaches are being explored in prostate cancer patients. This review provides a short overview of the various approaches. However, apart from the vaccine sipuleucel-T which has received approval from the US Food and Drug Administration (FDA), the majority of other approaches have still not reached phase 3 clinical trials.Rak prostate po incidenciji i mortalitetu spada među najčešće tumore u muškaraca. Usprkos nedavnim postignućima u liječenju hormonski rezistentnog raka prostate, i dalje postoji potreba istraživanja i pronalaženja lijekova koji mogu omogućiti kvalitetnu dugotrajnu remisiju metastatske bolesti ili izlječenje. Posljedično, istraživanja uključuju i razne imunoterapijske pristupe. U prikazanom radu dan je kratak pregled imunoterapijskih pristupa. Međutim, osim vakcine sipuleucel-T, koja je adobrena od američke agencije za hranu i lijekove, većina drugih imunoterapijskih pristupa nije ušla u treću fazu kliničkog ispitivanja

Imunoterapija tumora: mehanizam djelovanja

The prospect of eff ectively treating cancer patients with immunotherapy is now becoming a clinical reality. This is a consequence of clinically relevant and successful results obtained by applying monoclonal antibodies against immune checkpoint inhibitor receptors and chimeric antigen receptor (CAR) T cell therapy to patients with otherwise lethal cancers. Despite this success, only a limited number of cancer types and a subset of cancer patients currently respond to these therapies. Eff orts are now made to increase the number of cancer types and patients that can be treated successfully. This is an overview of the various approaches taken to this end.Klinička imunoterapija onkoloških bolesnika je postala klinička realnost. To je posljedica klinički relevantnih i uspješnih rezultata dobivenih primjenom monoklonskih protutijela protiv imunoloških kontrolnih molekula funkcije inhibitornih receptora te T-limfocita s kimeričnim antigenskim receptorima. Usprkos tim uspješnim i obećavajućim rezultatima, rezultati su postignuti samo protiv dijela tumora i opet u samo dijela bolesnika se postiže terapijski odgovor. U prikazanom radu dan je kratak pregled tih raznih imunoterapijskih pristupa

Imunoterapija raka debeloga crijeva

Recent successful results of a relatively new immunotherapeutic anti-cancer strategy based on the blockade of immune inhibitory pathways by monoclonal antibodies against checkpoint molecules can be considered as a medical breakthrough in clinical cancer immunotherapy. This type of immunotherapy became a standard part of systemic therapy protocols in the treatment of some metastatic solid tumors such as melanoma, non-small cell lung cancer, genitourinary cancers, Merkel-cell carcinoma, squamous-cell carcinoma of the head and neck, and solid tumors with DNA high microsatellite instability or DNA mismatch-repair deficiency. Recent progress in colorectal cancer genome analysis, and also supported by clinical observations, indicates that patients with DNA mismatch repair deficiency or microsatellite instability-high metastatic colorectal cancers are a distinct biomarker-defined population that might benefit from immunotherapy treatment with monoclonal antibodies against checkpoint molecules. This treatment has therefore become a new treatment option for this colorectal cancer subgroup of patients. However, besides tumor microsatellite instability or mismatch-repair deficiency status, other predictive biomarkers are also needed since not all these tumors respond to anti-check point immunotherapy treatment. This paper aims to present a basic overview of immunotherapy in mismatch repair deficient colorectal cancer patients.Nedavni uspješni rezultati razmjerno novog imunoterapijskog pristupa baziranog na blokadi imunoloških inhibitornih molekularnih puteva s monoklonskim antitijelima protiv molekula kontrolnih točaka mogu se smatrati medicinskim iskorakom u kliničkoj onkologiji. Taj tip imunoterapije postao je standardni dio protokola sistemne terapije nekih metastatskih tumora poput melanoma, raka nemalih stanica pluća, genitourinarnog karcinoma, karcinoma Merkelovih stanica, raka pločastih stanica glave i vrata i solidnih tumora s visokom mikrosatelitskom nestabilnošću ili manjkom popravka krivo sparenih baza DNA. Noviji rezultati molekularnih analiza genoma raka debelog crijeva, također poduprti kliničkim opažanjima, upućuju na to da su bolesnici s karcinomima u kojih postoji izražena mikrosatelitska nestabilnost ili nemogućnost popravka krivo sparenih baza DNA zasebna biomarkerom definirana populacija koja može imati koristi od liječenja monoklonskim antitijelima protiv imunoloških molekula kontrolnih točaka. Na temelju tih rezultata taj je imunoterapijski pristup postao nova terapijska opcija za tu podskupinu bolesnika s kolorektalnim rakom. Pa ipak, uz mikrosatelitsku nestabilnosti ili nemogućnost popravka krivo sparenih baza DNA potrebni su i drugi biomarkeri jer je taj imunoterapijski pristup učinkovit samo u dijelu tih bolesnika. Cilj je ovoga rada dati osnovni prikaz imunoterapije u tih bolesnika

Recent advances in clinical anti-cancer immunotherapy

Recent successful results with the relatively novel immunotherapeutic anti-cancer strategies such as adoptive T cell transfer (ACT), engineered T cells with chimeric antigen receptors (CARs), therapeutic Sipuleucil-T vaccine and checkpoint blockade inhibitors, do indicate that patient’s immune system can be effectively used against autologous tumor cells. Interactions between the immune system and the malignancy are complex but the results obtained using the above mentioned therapeutic approaches indicate acceptable clinical utility, efficacy and safety against several types of cancer. Much work still lies ahead but the success achieved with these modern immunotherapies is undeniable. This paper aims to present a short basic overview of these recent advances in cancer immunotherapy, but one should keep in mind that this field is in a dynamic stage given its success and that many immunotherapeutic agents, not all of them mentioned, are undergoing active clinical testing

Recent advances in clinical anti-cancer immunotherapy

Recent successful results with the relatively novel immunotherapeutic anti-cancer strategies such as adoptive T cell transfer (ACT), engineered T cells with chimeric antigen receptors (CARs), therapeutic Sipuleucil-T vaccine and checkpoint blockade inhibitors, do indicate that patient’s immune system can be effectively used against autologous tumor cells. Interactions between the immune system and the malignancy are complex but the results obtained using the above mentioned therapeutic approaches indicate acceptable clinical utility, efficacy and safety against several types of cancer. Much work still lies ahead but the success achieved with these modern immunotherapies is undeniable. This paper aims to present a short basic overview of these recent advances in cancer immunotherapy, but one should keep in mind that this field is in a dynamic stage given its success and that many immunotherapeutic agents, not all of them mentioned, are undergoing active clinical testing

Kolorektalni rak – uvodnik

This introductory type of article provides a brief overview of the current clinical status of sporadic colorectal cancer (CRC). CRC ranks as one of the most prevalent and incident cancers and is also between the deadliest ones worldwide, along with lung and breast cancers. A majority of CRCs are sporadic, with age being the most important risk factor. CRC appears to be a complex, heterogeneous disease that involves multiple signaling pathways and tumors that appear histologically identical may have different prognoses and different responses to treatment. CRC develops through gradual accumulation of genetic and epigenetic changes, resulting in the transformation of normal colonic mucosa into invasive cancer. Basically, the treatment for colorectal cancer varies by tumor location, stage at diagnosis and patient’s general condition. Any available data about the genes and/or molecular pathways that regulate activities such as cell growth, death or apoptosis, DNA repair, malignant alteration, etc. should also be taken into consideration. Recent polychemotherapy protocols along with the use of inhibitors of the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) pathways have enhanced the therapeutic responses and potentially also the patient prognoses. The treatment of CRC is expected to become more and more routinely based on identified molecular CRC subtypes and on validated prognostic and predictive biomarkers relatively soon (within several years), which should provide to patients better therapeutic outcomes with less side-effects.U prikazanom uvodnom radu dan je kratak pregled kliničkih aktualnosti u sporadičnom kolorektalnom raku (KR). KR je u svijetu, zajedno s rakom pluća i rakom dojke, jedan od najčešćih tipova raka kako po incidenciji tako i u prevalenciji. Nažalost, među zloćudnim tumorima je jedan i od češćih uzroka smrti. Većina KR je sporadična, s dobi kao jednim od najvažnih faktora rizika. Dijagnoza kolorektalnog raka bazira se na patohistološkim karakteristikama, ali rezultati molekularnih istraživanja ukazuju da se radi o skupini heterogenih tumora, koji se razlikuju u patogenezi, molekularnim aberacijama, prognozi i odgovoru na primijenjeno liječenje. KR se razvija kroz postepenu akumulaciju genskih i epigenetskih promjena, s posljedicom transformacije normalni stanica mukoze u invazivni rak. Strategija liječenja raka kolorektuma se prvenstveno temelji na smještaju tumora, procjeni uznapredovalosti i proširenosti tumora te općem stanju bolesnika. Ipak, sve češće kada je moguće, u obzir se uzimaju geni i/ili molekularni putevi koji reguliraju aktivnosti kao npr. rast i diobu stanica, njihovu smrt ili apoptozu, popravak molekula DNA, i druge slične stanične aktivnosti. Razmjerno noviji polikemoterapijski protokoli kao i uporaba inhibitora vaskularnog endotelijalnog faktora rasta i receptora za epidermalni faktor rasta poboljšali su liječenje, a moguće i prognozu bolesnika. Za očekivati je da će se unutar nekoliko slijedećih godina liječenje bolesnika s kolorektalnim rakom sve više i više temeljiti na nalazu molekularnih subtipova raka i prema validiranim prognostičkim i prediktivnim parametrima, jer bi takav pristup trebao osigurati bolju terapijsku učinkovitost i manje nuspojava