Clinical Oncology

[Molecular profi les in therapeutic strategy]

PETÁK István, SCHWAB Richárd

MAY 20, 2014

Clinical Oncology - 2014;1(02)

[In 2013, 10 years after the completion of the human genome, the cancer genome project has identifi ed almost all possible cancer genes, which could be responsible for the malignant transformation and progression. These genes are called „driver” genes, and the pathogenic mutations to be „driver” mutations. The census of „driver genes” in 2013 counted 138 genes and 1.5 million mutations. The situation is further complicated by the fact that up to 8 „driver” gene can be activated simultaneously in the same tumor, furthermore, the profi le may change during tumor growth and metastatization. 2013 was a turning point also because several targeted therapies were registered. Currently there are about 30 targeted drugs in clinical use and more than 200 targeted compounds in clinical development. This means that in 3-4 years the number of drugs will at least double. Most of the current patients can only access these compounds in clinical trials. But, patient already benefi t signifi cantly more even from phase I clinical trials, if they are selected based on the molecular profi le of the tumor. Fortunately, the advancements of next generation sequencing technologies provide the opportunity to identify all „driver” genes, - the whole molecular profi le, - in the patient’s tumor for the cost of one month targeted therapy. But the information generated can be only used in clinical practice if the results are processed by „molecular info-bionics”.]



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Clinical Oncology

[Neoadjuvant therapy in breast cancer – an update]

KAHÁN Zsuzsanna, RUSZ Orsolya, UHERCSÁK Gabriella, NIKOLÉNYI Alíz

[Traditionally, neoadjuvant systemic therapy (NST) serves as treatment of advanced breast cancer to achieve technical operability by resulting in tumor regression. Nowadays, NST is advantageous in all cases if adjuvant systemic therapy is needed, since the in vivo study of its effect provides possibility for the estimation of prognosis, the treatment may be modifi ed according to the therapeutic response, the systemic therapy starts earlier as compared to adjuvant therapy, and fi nally, it may result in the reduction of surgical and radiotherapeutical radicality. The type of NST should be selected on the basis of tumor features refl ecting treatment sensitivity. In case of chemosensitive cancers, chemotherapy is taxane- and anthracycline-based, and the planned dose should be delivered prior to surgery. In HER2-positive cancers, the addition of an anti-HER2 agent doubles the rate of pathological complete regressions. In hormone-sensitive tumors, the standard neoadjuvant endocrine therapy consists of an aromatase inhibitor (postmenopause), or tamoxifen or an aromatase inhibitor combined with an LHRH analog (premenopause) for 4-8 months that is continued following the surgery in the adjuvant setting. For the early evaluation of the effect of NST, serial tumor biopsy or imaging studies (MRI, PET) seem promising. Sentinel lymph node biopsy around the NST should be practiced with prudence; it may warrant the avoidance of axillary blockdissection in some cases. For the design of radiotherapy, the initial stage and the degree of regression are considered.]

Clinical Oncology

[Management of prostate cancer today]

PETRÁNYI Ágota Eszter, BODROGI István

[Although metastatic prostate cancer remains an incurable disease, the past years witnessed an extraordinary progress in the management of patients with castration resistant prostate cancer (CRPC). Development of novel agents that modulate the androgen receptor pathway, growth factor signaling pathways, immune functions and bone targeting machinery has been the focus of therapeutic strategies because of its signifi cance in the biology of prostate cancer progression. The arrival of several new agents — cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, denosumab and radium-223 — is changing the options and management of patients with metastatic castration resistant prostate cancer (mCRPC). Prostate cancer is a heterogeneous disease, therefore, in treatment must be considered the clinical characteristics of the disease as it manifests in an individual patient. The aim of this review is to summarize the most important new fi ndings for metastatic prostate cancers according to the different molecular pathways and to discuss their potential role on the management of this disease.]

Clinical Oncology

[Complex medical treatment of non small cell lung cancer - new challenges, new possibilities]


[Previously, it was suffi cient to differentiate small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC) in the decision making process for the therapeutic strategy of lung cancer. Recently, the situation has changed signifi cantly. There are only few new cytotoxic agents, and platinum based chemotherapy remains the standard combination in the treatment of NSCLC. In the last decade no further development has been discovered in the treatment of SCLC. However, the new molecular diagnostic and therapeutic possibilities have altered dramatically the management of NSCLC. NSCLC could not be considered as a separate entity anymore. The complex medical treatment of advanced NSCLC includes the molecular target driven therapies the histopathological subtype based chemotherapies and the immunotherapy. Immunotherapy is a new challenge in the treatment of lung cancer. Tumor-vaccines, inhibition of immune checkpoint pathways are investigated in clinical trials. Ongoing studies will defi ne the true effi cacy of these drugs. The complex combination of genes, proteins, different molecular pathways and patients characteristics, called “panomics”, are all parts of the treatment of lung cancer in the daily clinical practice.]

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[EGFR family and gynecologic cancers]


[The HER family of receptor tyrosine kinases may potentially play an important role in gynecologic malignancies. Amplifi cation and overexpression of various HER family members including epidermal growth factor receptor (EGFR/HER1) and HER2 have been reported in epithelial ovarian cancer and endometrial carcinoma as well as in cancer of the uterine cervix. High expression of EGFR has been associated with poor prognosis independent from histiotype while HER2 expression may be more histotype dependent. This review summarizes the clinical experience with anti EGFR/HER2 directed monoclonal antibody therapy in the three major gynecologic cancer types to date.]

Clinical Oncology

[Thromboprophylaxis in cancer patients]


[Cancer- and chemotherapy-associated venous thromboembolism (VTE) is a serious complication in patients with malignancies. Most important questions and challenges are summarized in the review and an attempt is made to answer some of them. Epidemiology, causes of thrombophilia and risk factor analysis including thrombogenicity of both tumorous disease and chemotherapy are discussed. The following special risk groups are detailed: (a) postoperative, (b) hospitalized non-surgical patients, (c) ambulatory patients with chemotherapy, (d) tumorous patients without chemotherapy. As conclusion, most important messages of the recent guidelines for preventing and treating cancer-associated thrombosis are discussed.]

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Clinical Oncology

[Radiological response evaluation of targeted therapy]


[The objective assessment of the changes in the tumor burden along with cancer therapy has essential importance. Recently, the quantitative evaluation of the radiological tumor response was undergone several changes. For conventional chemotherapy of solid tumors the standard procedure has been RECIST since 2000. The targeted therapies trigger other pathophysiological changes in the cells than the cytotoxic agents, accordingly the morphological changes show a new picture. Therefore the targeted therapies require a new evaluation system, that takes into consideration not only the tumor size, but other changes as well, the changes of attenuation that corresponds with the proportion of the viable cells. In case of the targeted therapies in substantial clinical was experienced even without signifi cant morphological changes in the tumour size. As a consequence, the traditional, size-based criteria system can underestimate the effi ciency of the new types of treatments. To eliminate this problem new evaluation systems were created taking the tumortypes and treatment protocolls into consideration. The estimation of the early tumor response to targeted therapy also has high importance. In assessment of the response functional imaging methods are used more frequently. The role of PET has already been defi ned in numerous tumortypes, however the determination of the position of some promising functional examinations still require further studies.]

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[Signaling pathways in cancer stem cells (Notch, Hedgehog, Wnt)]


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[Immuno(onco)therapy – road to the future]

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[Our immune system fi ghts effectively against infections, but the same activity exists against invading cancer cells, as well. However, malignant tumors are able to escape from these mechanisms; therefore tumor cells become unrecognizable for the immune system. Immuno-oncology is a novel and innovative discipline, focusing on a long-term purpose: to enhance the immune-response against malignancies. The main goal is to stimulate the immune system to properly recognize and destroy malignant tumor cells. This approach is comprehensive, includes the initiation of antitumor immune-response and enhancing its controlling mechanisms, moreover, provides active, anti-tumor effector cells. Recent results of anticancer research highlighted a new era of oncology, which is based on targeted, personalized medicine over cytotoxic therapies, and mainly focusing on the rapidly evolving discipline of immuno-oncology.]