Chemoterapie je jednou ze základních léčebných metod používaných v léčbě zhoubných nádorových onemocnění. V kombinaci s ostatními léčebnými modalitami dosahuje vynikajících výsledků. Cytostatika se liší různými mechanismy účinku. Jejich neselektivita a toxicita vede ke snaze identifikovat nové molekuly, které by posunuly terapeutické možnosti onkologie. Snahou je vytvořit takové látky, které by využívaly rozdílné pochody mezi zdravými a nádorovými buňkami a snažily se o diferencovanost zásahu. Hormonální terapie je další z onkologických systémových léčebných modalit. Pracuje na principu přítomnosti specifického znaku na nádorové buňce a jeho interakci s hormonálním preparátem. Klinická data prokázala efektivitu hormonální terapie pouze u karcinomu prostaty, karcinomu mléčné žlázy a karcinomu endometria.
Chemotherapy is one of the basic treating modalities applied in the treatment of malignant tumours. It reaches excellent effects in combination with other treating modalities. Cytostatics differ in their mechanisms of effect. Their non-selectivity and toxicity results into effort to identify new molecules that would shift forward therapeutical possibilities of oncology. The effort is to create such substances utilizing different procedures between healthy and oncogenous cells and to try to produce differentiated affect. Hormonal therapy is another oncological system treating modalities. It works on the principle of the presence of a specific feature found on the tumorous cell and its interaction with hormons. Clinical data have proved effectiveness of hormonal therapy only in the prostate cancer, breast cancer and endometrial cancer.
- Keywords
- Ixabepilon, Alimta,
- MeSH
- Diphosphonates pharmacology MeSH
- Epothilones administration & dosage therapeutic use MeSH
- Glutamates therapeutic use MeSH
- Guanine analogs & derivatives therapeutic use MeSH
- Humans MeSH
- Neoplasm Metastasis drug therapy MeSH
- Tubulin Modulators administration & dosage therapeutic use MeSH
- Bone Neoplasms drug therapy MeSH
- Neoplasms drug therapy MeSH
- Antimetabolites, Antineoplastic administration & dosage MeSH
- Antineoplastic Agents administration & dosage MeSH
- Selective Estrogen Receptor Modulators therapeutic use MeSH
- Tamoxifen administration & dosage MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Transplantable mouse methylcholanthrene- induced fibrosarcoma (CMC4 tumour growing in CBA/HZgr mice), characterized by lung metastases developing shortly after local tumour cell transplantation, was used as an experimental model to investigate the problem of tumour metastases after local tumour treatment. Surgery and/or irradiation were performed on locally growing tumour of particular size. Further, heavily irradiated, viable but not dividing tumour cells, imitating the situation in treated tumour-bearing organism, were injected intraperitoneally in a parallel group of treated tumour-bearing mice. The animals were killed 35 days after tumour transplantation and the number and volume of lung metastases were determined. Depending on the treatment performed, when the tumour mass was reduced or even eliminated, the number of lung metastases and their volume were significantly lower than in control mice, but the addition of tumour mass (injection of heavily irradiated tumour cells) resulted in a significant increase in lung metastases parameters, pointing to a possible role of the host's immune reaction against the tumour. Further, the release of a simple molecule, such as nitric oxide, from tumour mass seems to be detrimental for the survival of tumour cells and subsequently their metastases through the induction of angiogenesis and possible suppression of immune reaction. Thus, complex mechanisms could be involved when a locally growing tumour is exposed to a particular therapeutic approach.
V léčbě karcinomů hlavy a krku se v poslední době uplatňují nové ozařovací techniky, indukční chemoterapie, a především cílená (biologická) léčba. V souladu s porozuměním biologii signálních cest uplatňujících se při vzniku a progresi nádorů došlo k objevu a zavedení nových terapeutických postupů, které jsou zaměřené na cíle specifické pro nádorové buňky. Z těchto postupů bylo v léčbě nádorů hlavy a krku dosaženo nejlepších výsledků při použití cetuximabu a jeho kombinace s radioterapií a/nebo chemoterapií. V této indikaci byly zkoušeny také další monoklonální protilátky, např. panitumumab, tyrosinkinázové inhibitory nebo inhibitory angiogeneze; studovány jsou též mnohé další látky. Do budoucna je třeba nalézt biomarkery, které by přispěly k individualizaci a optimalizaci terapie.
The therapy of head and neck cancer has lately employed new irradiation techniques, induction chemotherapy, and most notably targeted (biological) therapy – in keeping with our growing understanding of the biology of signal pathways involved in the development and progression of tumours new therapies aimed at targets specific for tumour cells have been discovered and introduced. Of these therapies, best results in the treatment of head and neck cancers were obtained with cetuximab and its combination with radiotherapy and/or chemotherapy. Agents examined in this indication have also included monoclonal antibodies, e.g. panitumumab, tyrosine kinase inhibitors, or angiogenesis inhibitors; ongoing research is involved with other substances as well. In the future, biomarkers are urgently needed that would contribute to individualization and optimisation of therapy.
- Keywords
- cílená terapie, inhibitory tyrosinkinázy,
- MeSH
- Biological Therapy economics methods trends MeSH
- Cetuximab MeSH
- ErbB Receptors antagonists & inhibitors MeSH
- Drug Evaluation statistics & numerical data MeSH
- Angiogenesis Inhibitors therapeutic use MeSH
- Protein Kinase Inhibitors therapeutic use MeSH
- Carcinoma diagnosis therapy MeSH
- Combined Modality Therapy methods trends MeSH
- Humans MeSH
- Disease Management MeSH
- Neoplasm Metastasis therapy MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Head and Neck Neoplasms diagnosis therapy MeSH
- Prognosis MeSH
- Antineoplastic Agents pharmacology therapeutic use MeSH
- Protein-Tyrosine Kinases antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
Cieľ: Poukázať na nedostatočnú spoľahlivosť veľkosti nádoru ako prognostického faktora u pacientov s malígnym melanómom choroidey a prezentovať novú potenciálnu liečbu hepatálnych metastáz. Metodika: Dve kazuistiky pacientov s malým melanómom choroidey. Výsledky: Prezentujeme dva prípady malých melanómov choroidey, u ktorých sa rozvinuli metastázy. Liečbu primárneho nádoru predstavovala v oboch prípadoch rádioterapia. Liečba metastáz u prvého pacienta pozostávala z kombinácie viacerých liečebných modalít, kým u druhého pacienta bola aplikovaná nová liečba stereotaktickou rádioterapiou, Cyberknife. Prvý pacient zomrel v dôsledku diseminácie metastáz 7,6 rokov od primárnej liečby napriek dobrej lokálnej kontrole nádoru. Druhý pacient zomrel 11,3 rokov od primárnej liečby z dôvodu neonkologického ochorenia s veľmi dobrým očným nálezom a s postupným zmenšovaním hepatálnej metastázy. Záver: Aj malý melanóm choroidey sa môže rozvinúť v metastatické ochorenie, a to s veľkým časovým odstupom od primárnej liečby. Na stanovenie rizikových faktorov metastatického rozsevu malých choroidálnych melanómov sú potrebné ďalšie štúdie. Stereotaktická rádioterapia Cyberknife sa javí ako sľubná liečebná metóda solitárnych hepatálnych metastáz.
Purpose: To present data pointing out that small tumour size might not be a sufficient predictor of good prognosis of choroidal melanoma and present a new promising therapy of hepatic metastasis. Methods: Retrospective, noncomparative case report of two patients with small choroidal melanoma. Results: Two cases of small choroidal melanoma which developed metastases are described. Both patients underwent radiotherapy of the primary tumour. Metastases were treated by combined therapy in patient 1 while in patient 2 a new therapeutic modality of stereotactic radiotherapy, Cyberknife, was applied. Patient 1 died from metastatic spread 7,6 years after primary therapy despite a very good local tumour control. Patient 2 died 11,3 years after primary therapy due to intercurrent disease with a very good local eye findings and hepatic metastasis in regression. Conclusion: Choroidal melanoma of a small size can develop into metastatic disease even long time after satisfactory primary treatment. Further studies are required to assess the risk factors of metastatic spread in small uveal melanomas. Cyberknife stereotactic radiotherapy seems to be a promising therapeutic method of a solitary hepatic metastasis.
- MeSH
- Diagnostic Techniques, Ophthalmological MeSH
- Combined Modality Therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis * therapy MeSH
- Choroid Neoplasms * diagnosis physiopathology radiotherapy MeSH
- Palliative Care MeSH
- Primary Prevention MeSH
- Prognosis MeSH
- Vision Screening MeSH
- Aged, 80 and over MeSH
- Neoplasm Staging MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Publication type
- Case Reports MeSH
Východiska: Pacienti se senzitivními EGFR mutacemi jsou již standardně léčeni tyrozinkinázovými inhibitory (TKI) 1. a 2. generace. Nicméně na tyto preparáty vzniká po čase rezistence, která je u více než poloviny případů zapříčiněna EGFR rezistentní mutací T790M. Osimertinib je nová léčebná možnost, jak ji překonat. Bohužel i na tento preparát po několika měsících léčby vzniká rezistence. Jednou z jejích příčin je EGFR mutace C797S, o které pojednává naše kazuistika. Případ: Naše kazuistické sdělení přináší průkaz postupného vývoje rezistence k EGFR-TKI u pacientky s delecí na exonu 19 genu EGFR. Nejprve na základě získané mutace T790M při léčbě afatinibem a posléze na podkladě mutace C797S při terapii osimertinibem. Též se věnujeme úvahám o překonání této rezistentní mutace jak pomocí EGFR-TKI 4. generace, tak i případnými alternativními postupy (chemoterapie, imunoterapie, kombinace EGFR-TKI starších generací). Rovněž zmiňujeme vzácný případ nemocné s metastázami na peritoneu po předchozí léčbě osimertinibem. Tento nepříznivý stav jsme se vzhledem k již zhoršenému výkonnostnímu stavu nemocné pokusili ovlivnit erlotinibem, který neumožňoval podání chemoterapie. Jsou doložené případy, kdy erlotinibem byli úspěšně léčeni pacienti s peritoneálními metastázami a též nemocní s EGFR mutací C797S po progresi na afatinibu. To však v našem případě nenastalo, patrně pro přetrvávající EGFR mutaci T790M. Závěr: V naší kazuistice erlotinib nejevil účinnost po progresi na osimertinibu. Jedinou možnou léčbou se v tomto případě prozatím jeví chemoterapie u pacientů v dobrém klinickém stavu. TKI nové generace procházejí nadějným vývojem.
Background: Patients with sensitive EGFR mutations are already being treated with first and second generation tyrosine kinase inhibitors (TKIs). However, resistance to these drugs occurs over time, and over half of all cases is caused by a mutation (T790M) in the EGFR kinase domain. Osimertinib offers a new treatment option that overcomes this problem. Unfortunately, resistance to this drug also develops after several months of treatment and is caused by another mutation (C797S) in EGFR. Case report: Our case report provides evidence for the progressive development of EGFR-TKI resistance in a patient with a deletion of exon 19 in the EGFR gene. First, based on a mutation (T790M) identified after afatinib treatment and a subsequent mutation (C797S) mutation identified after osimertinib treatment. We mention overcoming this resistance (C797S) mutation by using 4th generation EGFR-TKI and other alternative procedures (chemotherapy, immunotherapy, and combinations of older EGFR-TKI generations). We also mention a rare case of peritoneal metastasis that occurred after previous treatment with osimertinib that we attempted to ameliorate by using erlotinib because the impaired condition of the patient did not allow treatment by chemotherapy. There are documented cases in which erlotinib has been successfully given to patients with peritoneal metastases and patients with the EGFR mutation C797S following progression to afatinib. This was not the case in our patient, probably because of the remaining EGFR mutation T790M. Conclusion: In our case report, erlotinib did not show efficacy after progression to osimetinib. Nowadays, chemotherapy is the only possible treatment in patients with good a performance status. The next-generation of TKIs are undergoing promising developments.
- Keywords
- osimertinib,
- MeSH
- Adenocarcinoma MeSH
- Chemotherapy, Adjuvant MeSH
- Afatinib MeSH
- Biopsy methods MeSH
- Gene Deletion MeSH
- Adult MeSH
- ErbB Receptors * genetics MeSH
- Fatal Outcome MeSH
- Immunohistochemistry MeSH
- Immunotherapy MeSH
- Drug Resistance * MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Mutation * MeSH
- Lung Neoplasms diagnosis complications therapy MeSH
- Pemetrexed therapeutic use MeSH
- Antineoplastic Agents MeSH
- Renal Insufficiency MeSH
- Protein-Tyrosine Kinases antagonists & inhibitors administration & dosage therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Diagnostic Techniques, Ophthalmological MeSH
- Combined Modality Therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis * therapy MeSH
- Choroid Neoplasms * diagnosis physiopathology radiotherapy MeSH
- Palliative Care MeSH
- Primary Prevention MeSH
- Prognosis MeSH
- Vision Screening MeSH
- Aged, 80 and over MeSH
- Neoplasm Staging MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Fluorometry methods MeSH
- Humans MeSH
- Neoplasm Metastasis diagnosis MeSH
- Bone Neoplasms metabolism physiopathology MeSH
- Prostaglandins metabolism MeSH
- Antibody Specificity MeSH
- Bone Marrow Examination MeSH
- Check Tag
- Humans MeSH
- Publication type
- Case Reports MeSH
Od uvedenia nových biologických cielených liekov (tyrozín-kinázových inhibítorov a mammalian target of rapamycin (mTOR) inhibítorov) do liečby renálneho karcinómu sme svedkami éry nových liečebných možností. U pacientov so vznikom mozgových metastáz pretrváva dilema ohľadne ďalšieho optimálneho liečebného postupu špeciálne u podskupiny pacientov bez progresie mimo centrálneho nervového systému. Cieľom prezentovanej kazuistiky je poukázať, že je možné pokračovať v tej istej liečbe cieleným liekom u pacienta po vzniku mozgových metastáz, ktorému bola aplikovaná lokálna rádioterapia na mozgové metastázy, s dosiahnutím zmysluplného celkového prežívania.
There is a new era of treatment options since introduction of new biological targeted therapies (tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors) in renal cell cancer. However, in patients who developed brain metastases, there is still treatment dilemma about an optimal therapeutic scenario, particularly in the subgroup of patients without disease progression outside the central nervous system. The objective of this case report is to present that it is possible to continue the same targeted therapy after development of brain metastasis after application of local whole brain irradiation with meaningful overall survival.
- MeSH
- Aphasia etiology MeSH
- Hypertension drug therapy MeSH
- Indoles therapeutic use MeSH
- Interferon-alpha MeSH
- Leukoencephalopathies MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Neoplasm Metastasis * therapy MeSH
- Kidney Neoplasms * complications therapy MeSH
- Brain Neoplasms * complications radiotherapy therapy MeSH
- Paresis MeSH
- Tomography, X-Ray Computed MeSH
- Survival MeSH
- Pyrroles therapeutic use MeSH
- Aged MeSH
- Protein-Tyrosine Kinases * antagonists & inhibitors MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
In addition to its ability to act as a promising inducer of tumor-specific cell death, TRAIL has also been shown to stimulate signaling pathways leading to cancer cell survival. We examined the changes of anti-apoptotic Mcl-1 protein level following TRAIL treatment of human cell lines representing different stages of colon carcinogenesis-adenocarcinoma (HT-29, HCT116) or secondary metastasis (SW620), together with cell line derived from human fetal colon (FHC). While TRAIL was capable of triggering an anti-apoptotic signaling leading to significant early ERK-mediated transcriptional up-regulation of Mcl-1 in selected colon adenocarcinoma cell lines, none or very limited effects were demonstrated in cell lines derived from colon lymph node metastasis or fetal colon, respectively. We demonstrated an immediate impact of Mcl-1 protein level manipulations on the course of early acute apoptotic response of colon adenocarcinoma cells to TRAIL. It is therefore essential to consider the dynamics of modulation of Mcl-1 level and the balance between TRAIL-induced pro- and anti-apoptotic pathways when predicting the response of cells in different stages of cancer development, and designing the anticancer therapy using TRAIL.
- MeSH
- Epithelial Cells metabolism MeSH
- Humans MeSH
- Neoplasm Metastasis pathology MeSH
- Cell Line, Tumor MeSH
- Colonic Neoplasms metabolism pathology MeSH
- TNF-Related Apoptosis-Inducing Ligand physiology MeSH
- Proto-Oncogene Proteins c-bcl-2 genetics MeSH
- Gene Expression Regulation MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
