Biodiesel production from jatropha oil by catalytic and non-catalytic approaches: an overview

Biodiesel (fatty acids alkyl esters) is a promising alternative fuel to replace petroleum-based diesel that is obtained from renewable sources such as vegetable oil, animal fat and waste cooking oil. Vegetable oils are more suitable source for biodiesel production compared to animal fats and waste cooking since they are renewable in nature. However, there is a concern that biodiesel production from vegetable oil would disturb the food market. Oil from Jatropha curcas is an acceptable choice for biodiesel production because it is non-edible and can be easily grown in a harsh environment. Moreover, alkyl esters of jatropha oil meet the standard of biodiesel in many countries. Thus, the present paper provides a review on the transesterification methods for biodiesel production using jatropha oil as feedstock

CDK4/6 Inhibitors: Promising Opportunities beyond Breast Cancer.

Patnaik and colleagues report on the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of abemaciclib for the treatment of advanced solid cancers, demonstrating antitumor activity in advanced breast cancers as well as glioblastoma, melanoma, non-small cell lung cancer, colorectal cancer, and ovarian cancer. The development of abemaciclib and other CDK4/6 inhibitors should now be fully optimized through the use of novel predictive biomarkers of response and rational combinations. Cancer Discov; 6(7); 697-9. ©2016 AACRSee related article by Patnaik et al., p. 740

Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics.

Precision medicine continues to be the benchmark to which we strive in cancer research. Seeking out actionable aberrations that can be selectively targeted by drug compounds promises to optimize treatment efficacy and minimize toxicity. Utilizing these different targeted agents in combination or in sequence may further delay resistance to treatments and prolong antitumor responses. Remarkable progress in the field of immunotherapy adds another layer of complexity to the management of cancer patients. Corresponding advances in companion biomarker development, novel methods of serial tumor assessments, and innovative trial designs act synergistically to further precision medicine. Ongoing hurdles such as clonal evolution, intra- and intertumor heterogeneity, and varied mechanisms of drug resistance continue to be challenges to overcome. Large-scale data-sharing and collaborative networks using next-generation sequencing (NGS) platforms promise to take us further into the cancer 'ome' than ever before, with the goal of achieving successful precision medicine

Combining Molecularly Targeted Agents: Is More Always Better?

The concurrent targeting of critical nodes along key signaling pathways with molecularly targeted agents is a rational antitumor strategy, which has had varying degrees of success. Combinatorial challenges include overcoming synergistic toxicities and establishing whether combinations are truly active, to make "go, no-go" decisions to proceed to later phase trials. Clin Cancer Res; 23(5); 1123-5. ©2016 AACRSee related article by Calvo et al., p. 1177

Targeting DNA Repair in Cancer: Beyond PARP Inhibitors

Germline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2-mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell-cycle checkpoint activation, trigger apoptosis, and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations. $\textbf{SIGNIFICANCE}$: Various inhibitors of DDR components are in preclinical and clinical development. A thorough understanding of DDR pathway complexities must now be combined with strategies and lessons learned from the successful registration of PARP inhibitors in order to fully exploit the potential of DDR inhibitors and to ensure their long-term clinical success. Cancer Discov; 7(1); 20-37. ©2016 AACRJ.S. Brown, B. O'Carrigan, and T.A. Yap acknowledge support from the Experimental Cancer Medicine Centre (to The Institute of Cancer Research) and the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research). Research in The Jackson laboratory is funded by Cancer Research UK (CRUK) program grant number C6/A18796. Core funding is provided by CRUK (C6946/A14492) and the Wellcome Trust (WT092096). S.P. Jackson receives his salary from the University of Cambridge, UK, supplemented by CRUK

Clinical brca1/2 reversion analysis identifies hotspot mutations and predicted neoantigens associated with therapy resistance

Reversion mutations in BRCA1 or BRCA2 are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 reversions. This identified reversion “hotspots” and “deserts” in regions encoding the N and C terminus, respectively, of BRCA2, suggesting that pathogenic mutations in these regions may be at higher or lower risk of reversion. Missense and splice-site pathogenic mutations in BRCA1/2 also appeared less likely to revert than truncating mutations. Most rever-sions were <100 bp deletions. Although many deletions exhibited microhomology, this was not universal, suggesting that multiple DNA-repair processes cause reversion. Finally, we found that many reversions were predicted to encode immunogenic neopeptides, suggesting a route to the treatment of reverted disease. As well as providing a freely available database for the collation of future reversion cases, these observations have implications for how drug resistance might be managed in BRCA-mutant cancers. SIGNIFICANCE: Reversion mutations in BRCA genes are a major cause of clinical platinum and PARP inhibitor resistance. This analysis of all reported clinical reversions suggests that the position of BRCA2 mutations affects the risk of reversion. Many reversions are also predicted to encode tumor neoantigens, providing a potential route to targeting resistance