Promoting patient engagement in cancer genomics research programs: An environmental scan.

Background: A national priority in the United States is to promote patient engagement in cancer genomics research, especially among diverse and understudied populations. Several cancer genomics research programs have emerged to accomplish this priority, yet questions remain about the meaning and methods of patient engagement. This study explored how cancer genomics research programs define engagement and what strategies they use to engage patients across stages in the conduct of research. Methods: An environmental scan was conducted of cancer genomics research programs focused on patient engagement. Research programs were identified and characterized using materials identified from publicly available sources (e.g., websites), a targeted literature review, and interviews with key informants. Descriptive information about the programs and their definitions of engagement, were synthesized using thematic analysis. The engagement strategies were synthesized and mapped to different stages in the conduct of research, including recruitment, consent, data collection, sharing results, and retention. Results: Ten research programs were identified, examples of which include the Cancer Moonshot Biobank, the MyPART Network, NCI-CONNECT, and the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. All programs aimed to include understudied or underrepresented populations. Based on publicly available information, four programs explicitly defined engagement. These definitions similarly characterized engagement as being interpersonal, reciprocal, and continuous. Five general strategies of engagement were identified across the programs: 1) digital (such as websites) and 2) non-digital communications (such as radio broadcasts, or printed brochures); 3) partnering with community organizations; 4) providing incentives; and 5) affiliating with non-academic medical centers. Digital communications were the only strategy used across all stages of the conduct of research. Programs tailored these strategies to their study goals, including overcoming barriers to research participation among diverse populations. Conclusion: Programs studying cancer genomics are deeply committed to increasing research participation among diverse populations through patient engagement. Yet, the field needs to reach a consensus on the meaning of patient engagement, develop a taxonomy of patient engagement measures in cancer genomics research, and identify optimal strategies to engage patients in cancer genomics. Addressing these needs could enable patient engagement to fulfill its potential and accelerate the pace of cancer genomic discoveries.

Hedgehog Pathway Inhibitors: Clinical Implications and Resistance in the Treatment of Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer and is on the rise. Most BCCs are benign; however, a very small percentage are locally advanced and metastatic. The pathway that normally regulates cell growth and proliferation is directed by the hedgehog pathway (HP). In BCC, it becomes over-stimulated due to genetic abnormalities. Treatments for BCC include local treatment by cryotherapy (liquid nitrogen), topical immunosuppression, surgery, or radiotherapy. Systemic treatment may be required in locally advanced lesions, metastatic BCC, or individuals who are inoperable. The systemic treatments of BCC act to inhibit the HP and are called hedgehog pathway inhibitors. The first one being vismodegib and the second sonidegib. Although these treatments have shown promising results, they have prominent side effects in almost all patients, with few patients having to discontinue the treatment. About 50% of patients did not respond to treatment from the beginning, some had partial responses, others had recurrence after discontinuing the drugs, and few had worsening of the disease. In this paper, we will explore the most common side effects, resistance, and different methods to overcome resistance to ensure the highest rate of cure for BCC.

Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

Fluorescence resonance energy transfer between polyphenolic compounds and riboflavin indicates a possible accessory photoreceptor function for some polyphenolic compounds.

The photoreceptive extreme tip of the wheat coleoptile exhibits intense green-yellow fluorescence under UV light, suggesting the presence of UV-absorbing materials. Fluorescence spectra of the intact coleoptile tip and tip homogenate showed the presence of the known photoreceptor pigments flavin and carotene, and a preponderance of phenolic compounds. Absorption spectra and fluorescence spectra of various phenolic compounds showed close overlap with the absorption and fluorescence spectra of the wheat coleoptile tip homogenate. Fluorescence spectra of several phenolic compounds showed close overlap with the absorption bands of flavin, carotene and pterine, suggesting possible energy transduction from phenols to these photoreceptors. Excitation of gentisic acid and ferulic acid with 340 nm light in the presence of flavin showed enhancement of flavin fluorescence in a concentration- and viscosity-dependent fashion, indicating fluorescence resonance energy transfer between them and riboflavin. Furthermore, several phenolic compounds tested generated superoxide anion on excitation at 340 nm, suggesting that superoxide-dependent signal cascades could operate in a polyphenol-mediated pathway. Phenolic compounds thus may act as accessory photoreceptors bringing about excitation energy transfer to the reactive photoreceptor molecules, or they may take over the function of the normal photoreceptor in genetic mutations lacking the system, or both processes may occur. The responses of plants to UV-B and UV-A light in mutants may be explained in terms of various phenolics acting as energy transducers in photoreceptor functioning.