Is the Patient Actually Failing on Enzalutamide? A Case Report and Issues to Consider in Enzalutamide-Resistant Oligoprogressive Metastatic Castrate-Resistant Prostate Cancer.

BACKGROUND: Metastatic castrate-resistant prostate cancer (mCRPC) is a challenging disease, especially in heavily pretreated patients. Androgen pathway inhibitors have contributed to a notable improvement in the overall survival and quality of life in patients with mCRPC during the last decade. Still, a considerable percentage of patients are unable to draw benefits from this drug category and are deprived of a treatment that offers limited toxicity and preserves a good quality of life. The mechanisms leading to this pre-existing or acquired resistance, as well as the possible strategies to overcome this resistance have been put at the center of scientists' attention. CASE PRESENTATION: With the present report we present the case of a 70-year-old patient with mCRPC, who was apparently an enzalutamide non-responder, but a multimodal approach with enzalutamide continuation and irradiation to his symptomatic oligoprogressive disease converted him to a responder with clinical, biochemical and imaging response; furthermore, we discuss the existing data providing evidence for the use of metastasis-directed therapy in combination with androgen pathway inhibitors in order to overcome drug resistance in patients with oligoprogressive disease. CONCLUSION: A considerable proportion of patients with oligometastatic or oligoprogressive prostate cancer who seem not to respond to androgen pathway inhibitors, such as enzalutamide, due to preexisting or acquired resistance, could benefit from MDT with a multimodal treatment approach. This strategy allows androgen pathway inhibitor continuation beyond biochemical progression and delays the switch to next-line systemic treatment.

Fourier Transform Infrared Spectroscopy in the Study of Discrimination of Lobular Breast Cancers.

BACKGROUND/AIM: The early diagnosis of breast cancer plays an important role in reducing mortality and optimizing the prognosis of the disease. The existing visual and histopathological methods do not give any information at a molecular level. Fourier transform infrared spectroscopy does not require any preparation, such as fixation and histological stains. The collected infrared spectral "biomarker bands" give information at a molecular level and could be used for biomarker screening, in order to minimize the false-positive or false-negative results. MATERIALS AND METHODS: For this prospective study, nine biopsies of lobular carcinoma (7 in situ and 2 invasive) and the adjacent healthy region of the biopsies were used. Each infrared spectrum consisted of 120 scans/spectrum (120 co-added spectra) at a spectral resolution of 4 cm -1 . RESULTS: The infrared spectral analysis revealed three important "diagnostic spectral regions" between 3,300-2,850 cm -1 , 1,700-1,500 cm -1 , and 850-800 cm -1 , which are related to membrane, collagen, and DNA configuration damage, respectively. The shift of the absorption band at 1,161 cm -1 at higher wave numbers up to 1,172 cm -1 is assigned to vC-O-C bonds due to membrane, protein, and DNA glycosylation. CONCLUSION: The "biomarker bands" at 1,172 cm -1 can be used as "diagnostic marker bands" for cancer progression. The shift of the absorbance band at 825 cm -1 of the native configuration of B-DNA to lower wavenumbers at 810 cm -1 Z-DNA in grade III, suggests the irreversible stage of the disease. The detection and possibility to differentiate the DNA structures may allow detection of carcinogenesis at the early stage of the disease, and development of new anticancer therapies.

Hormesis Shifts the No-Observed-Adverse-Effect Level (NOAEL).

Data from recent dose-response toxicological studies suggest that the no-observed-adverse-effect-level (NOAEL) may depend upon whether hormesis is present. A further examination of these data supports this hypothesis by showing that the NOAEL was greater for living units (organisms or cells) showing hormesis than for living units showing no hormesis. For example, some cancer tissue cells may exhibit hormetic responses to an anticancer drug while some other cancer tissue cells may not. These findings suggest that living units showing hormesis may also be less susceptible than living units not showing hormesis. However, these findings are preliminary and cannot be generalized or assumed to be a norm yet. New studies are needed to evaluate how NOAEL shifts depending on the occurrence of hormesis.

Oxidative stress in ageing and disease development studied by FT-IR spectroscopy.

FT-IR spectroscopy was used to investigate the effect of oxidative stress and to approach the mechanism on cancer bone demineralization, aortic valve mineralization and heterotopic ossification on disease development. The FT-IR spectra obtained from paediatric, adult bone and ex vivo irradiated adult healthy bone with a dose of 20Gy were compared with those of healthy bone. The increase of band intensity changes of vasCH2,vsCH2 in the region 3000-2850cm-1 depended on aging, the disease progression and the dose of irradiation. The bands at 3080cm-1 and 1744cm-1, which originate from olefinic terminal bond (v=CH) and ester carbonyl group (vROCO), respectively, indicate the influence of oxidative stress on lipid degradation and peroxidation, respectively. The new bands at about 1690cm-1 and 1516cm-1 denote the presence of ß-sheet conformation of the proteins due to the diseases, confirming the increasing amount of lipophilic environment and fibril formation. Comparison of the FT-IR spectra of calcified aortic valve and hip heterotopic ossification with that of normal bones showed that in the bone-like formation the peroxide anion free radicals play an important role in the disease.

An FT-IR Spectral Analysis of the Effects of γ-Radiation on Normal and Cancerous Cartilage.

In the present study we used non-distractive physicochemical methods to investigate the effect of γ-radiation on human articular cartilage. Comparison between the FT-IR (Fourier transform infrared) spectra before and after irradiation of the cartilage with different doses of radiation showed considerable changes in the spectra. It was found that for doses up to 2 Gy the collagen helices changed their structure from α-helix to random coil. By increasing the radiation dose it was found that the proteins' structure changed further to amyloid-like protein formation and to fragments of glycosaminoglycan chains, which were indicated in the IR spectra. Furthermore, comparison between the spectra of normal and irradiated cartilage, cancerous cartilage and cartilage from patients who received radiotherapy showed similarities in the spectra together with the formation of an aldehyde absorption band at 1740 cm(-1) suggesting that in all cases of cartilage examined,oxidative stress played major role in the damage progression of cartilage.