National Cancer Institute's 'RAS Project' Takes Aim at Common Cancer-Driving Protein

The National Cancer Institute (NCI) is organizing a massive collaborative initiative between its laboratory and hundreds of outside researchers to discover cancer treatments targeting a class of genes called RAS genes and their products, RAS proteins. RAS genes, including their most common form, KRAS, are mutated in one-third of all cancers. Although the important role of RAS in cancer has been known for over 30 years, no treatments targeting RAS have been developed so far, because RAS proteins lack a ‘binding site’ where drugs could attack. However, recent research has uncovered potential weaknesses in RAS that future treatment might exploit. The NCI’s RAS Project aims to ‘crowdsource’ the expertise of many researchers to better understand and tackle RAS.


National Cancer Institute's 'RAS Project' Takes Aim at Common Cancer-Driving Protein

The National Cancer Institute (NCI) is organizing a massive collaborative initiative between its laboratory and hundreds of outside researchers to discover cancer treatments targeting a class of genes called RAS genes and their products, RAS proteins. RAS genes, including their most common form, KRAS, are mutated in one-third of all cancers. Although the important role of RAS in cancer has been known for over 30 years, no treatments targeting RAS have been developed so far, because RAS proteins lack a ‘binding site’ where drugs could attack. However, recent research has uncovered potential weaknesses in RAS that future treatment might exploit. The NCI’s RAS Project aims to ‘crowdsource’ the expertise of many researchers to better understand and tackle RAS.


U.S. Cancer Institute 'Megaproject' to Target Common Cancer-Driving Protein

“It may be dealing with the worst budget crunch in its history, but that is not stopping the National Cancer Institute (NCI) from doing new things. Today, NCI officials outlined a plan to bring together the agency’s contract lab in Frederick, Maryland, and outside researchers to find ways to block a mutated protein that drives growth in one-third of all cancers but was thought impossible to “drug” until now.”


U.S. Cancer Institute 'Megaproject' to Target Common Cancer-Driving Protein

“It may be dealing with the worst budget crunch in its history, but that is not stopping the National Cancer Institute (NCI) from doing new things. Today, NCI officials outlined a plan to bring together the agency’s contract lab in Frederick, Maryland, and outside researchers to find ways to block a mutated protein that drives growth in one-third of all cancers but was thought impossible to “drug” until now.”


U.S. Cancer Institute 'Megaproject' to Target Common Cancer-Driving Protein

“It may be dealing with the worst budget crunch in its history, but that is not stopping the National Cancer Institute (NCI) from doing new things. Today, NCI officials outlined a plan to bring together the agency’s contract lab in Frederick, Maryland, and outside researchers to find ways to block a mutated protein that drives growth in one-third of all cancers but was thought impossible to “drug” until now.”


Biomarker-Guided Targeted Therapy Is Becoming a Reality

A massive database study performed recently in France demonstrates that genetic testing of non-small cell lung cancer (NSCLC) tumors for disease-relevant biomarkers is feasible, and indeed already helps guide treatment strategies for patients. France’s National Cancer Institute funds routine assessment of genetic alterations in six genes for NSCLC patients: EGFR, KRAS, ALK, BRAF, HER2, and PI3K. Since April 2012, these genetic analyses have been collected into a database. By now, biomarker assessments have been performed for 10,000 NSCLC patients. Of the patients for whom treatment data was available, over half received therapies guided directly by their biomarker testing profile. For example, over half of patients who were found to have a mutation in the EGFR gene were treated with EGFR inhibitors. As the database continues to grow, researchers recommend that newer biomarkers, like the ROS1 gene, should be added to the analysis. Furthermore, they urge that the availability of clinical trials of biomarker-targeted treatments needs to be increased.


ALK Rearrangements are Mutually Exclusive with Mutations in EGFR or KRAS: An Analysis of 1683 Patients with Non-Small Cell Lung Cancer

Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small cell lung cancer (NSCLC). Recently, several case reports and small series have reported that ALK rearrangements can overlap with other oncogenic drivers in NSCLC in crizotinib-naïve and resistant cancers. Our study here shows that functional ALK rearrangements were mutually exclusive with EGFR and KRAS mutations in a large Western patient population. This lack of overlap was also observed in ALK-positive cancers with acquired resistance to crizotinib.


Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a target in LKB1 Mutant Lung Cancer

We employed an integrative approach to define novel therapeutic targets in KRAS-driven LKB1 mutant lung cancers. LKB1 mutant lung cancers have deficits in nucleotide metabolism conferring hypersensitivity to DTYMK inhibition, suggesting that DTYMK, encoding deoxythymidylate kinase which catalyzes dTTP biosynthesis, is a potential therapeutic target in this aggressive subset of tumors.


Coordinate Direct Input of Both KRAS and IGF1 Receptor to Activation of PI3 kinase in KRAS-Mutant Lung Cancer

“Using a panel of non–small cell lung cancer (NSCLC) lines, we show here that MAP-ERK kinase (MEK) and RAF inhibitors are selectively toxic for the KRAS-mutant genotype, whereas phosphoinositide 3-kinase (PI3K), AKT, and mTOR inhibitors are not. IGF1 receptor (IGF1R) tyrosine kinase inhibitors also show selectivity for KRAS-mutant lung cancer lines.”