Could a Growth Inhibitory Factor, Present Only during Pregnancy, be Made Available to Treat Cancer in Adults? A Commentary

Human alpha-fetoprotein (AFP) is well-known as the “gold standard” biomarker for liver and germ cell tumors. It has also been utilized as a pregnancy screening analyte for neural tube defects as well as Down syndrome, when combined with other gestational-age dependent biomarkers. However, a lesser known and recognized property of AFP is its role in the maintenance and monitoring of fetal growth during ontogenetic development in man. Although a major function of AFP during pregnancy involves the serum transport of estrogens, fatty acids, retinoid, and other compounds, the positive and negative regulation of fetal growth is a vital additional function of AFP. Human AFP largely functions as a growth promoting agent; however, the fetal protein is able to temporarily convert to a growth inhibitory factor in stress and shock environments in the fetal milieu. The development of a transient form of AFP or its derived peptides could be harnessed for use as an adjunct therapeutic agent to treat cancer in adults.

Disintegrin-Like Peptides Derived from Naturally-Occurring Proteins: A Proposed Adjunct Treatment for Cancer Therapy: A Commentary

Disintegrins constitute a group of small proteins or peptides (45-85 amino acids) that function as natural antagonists of integrin receptor-dependent cell activities. The integrins themselves comprise a superfamily of hetero-dimeric (alpha and beta chains) transmembrane cell surface receptors whose functions include cell adhesion, growth, migration, and angiogenesis. In contrast, the disintegrins comprise groups of two types of molecules, namely, a) short proteins or peptides comprising insect and animal venoms; and b) intrinsic sub domain sequence fragments or short motifs present on large mammalian metalloprotease enzymes. Certain disintegrins bind specifically to tri-amino acid sequences (RGD, LGD etc) located on integrins beta-1 and beta-3 chains of the hetero complex receptors. Binding at such sites can inhibit or block cell migration, angiogenesis, metastasis, and platelet aggregation. Recently, small disintegrin-like peptides from naturally-occurring proteins have likewise been reported to inhibit growth and adhesion functions associated with integrin-dependent cell activities. The present report describes examples of such disintegrin-like peptides and provides support for their proposed use in adjunct cancer therapy.

Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.