Future oncology
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Everolimus (RAD001), a mTOR inhibitor, was initially used as an immunosuppressant in organ transplant patients; however, it also has significant antineoplastic properties. In patients with subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis complex who are not candidates for surgery, single-agent everolimus has demonstrated the ability to significantly reduce SEGA volume with good tolerability. In the Phase III, randomized, placebo-controlled trial, everolimus was associated with a SEGA response rate of 35% compared with 0% in the placebo group. The most common adverse events in clinical trials were stomatitis/mouth ulceration and upper respiratory tract infections, and most adverse events were grade 1 or 2; grade 4 events were rare.
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As antineoplastic treatments have become more successful, an increasing number of women with cancer survive to endure the long-term consequences of chemotherapy. One of the most important of these consequences in young females is premature ovarian failure and infertility. Owing to increasing survival rates, many of these young women are seeking methods to preserve their fertility. ⋯ In vitro maturation of oocytes is an attractive alternative for fertility preservation in cancer patients because it does not require ovarian stimulation and it can be performed at any time of the menstrual cycle. In addition, this technique can be combined with ovarian tissue cryobanking. In this review, we discuss the position of in vitro maturation of oocytes in the fertility preservation strategy in young women.
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Malignant pleural mesothelioma is a rare malignancy with a dismal prognosis. The clinical management of most of the patients with this disease is quite challenging, and, overall, the therapeutic strategy has not yet benefited from the recent advances in molecular biology. Randomized evidence supports the use of cisplatin in combination with pemetrexed or raltitrexed as first-line treatments. ⋯ The role of second-line chemotherapy is unproven, although pemetrexed can be regarded as the standard option in pemetrexed-naive patients and therapeutic rechallenge with pemetrexed may be considered in selected patients with prolonged disease control after first-line therapy. Targeted therapies failed to demonstrate any substantial activity; however, immunotherapies may complement other treatment strategies. In summary, there is an unmet clinical need and innovative approaches to select new potentially active drugs are highly warranted.
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The anticancer agent 3-aminopyridine-2-carboxaldehyde thiosemicarbazone is a ribonucleotide reductase inhibitor. It inactivates ribonucleotide reductase by disrupting an iron-stabilized radical in ribonucleotide reductase's small subunits, M2 and M2b (p53R2). Unfortunately, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone also alters iron II (Fe(2+)) in hemoglobin. ⋯ This balance may be perturbed by symptomatic toxicity levels during 3-aminopyridine-2-carboxaldehyde thiosemicarbazone therapy. Indications of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone sequelae attributable to methemoglobinemia include resting dyspnea, headaches and altered cognition. Management of methemoglobinemia includes supplemental oxygen, ascorbate and, most importantly, intravenously administered methylene blue as a therapeutic antidote.
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The goal of effective population-based screening for ovarian cancer remains elusive despite intense efforts aimed at improving upon biomarker and imaging modalities. While dozens of potential serum biomarkers for ovarian cancer have been identified in recent years, none have yet overcome the limitations that have hindered the clinical use of CA-125. Avenues of opportunity in biomarker development are emerging as investigators are beginning to appreciate the significance of remote, as well as local or regional, sources of biomarkers in the construction of diagnostic panels, as well as the importance of evaluating biomarkers in prediagnostic settings. ⋯ Such refinements must take into account both the bioinformatic and biological significance of each candidate. Approaches incorporating these considerations may potentially overcome the challenges to early detection posed by the histological heterogeneity of ovarian cancer. Here, we review the recent progress achieved in efforts to develop diagnostic biomarker panels for ovarian cancer and discuss the challenges that remain.