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Our understanding of tumorigenesis and cancer progression as well as clinical therapies for different cancer types have evolved dramatically in recent years. However, even with this progress, there are big challenges for scientists and oncologists to tackle, ranging from unpacking the molecular and cellular mechanisms involved to therapeutics and biomarker development to quality of life in the aftermath of therapy. In this article, we asked researchers to comment on the questions that they think are important to address in the coming years., Competing Interests: Declaration of interests R.B. is a shareholder of Agendia and Oncosence, is a member of the board of directors for and has received research funding from Lixte Biotechnology holdings, and receives research funding from Heparegenix GmbH. J.A.J. has received honoraria for speaking at research symposia organized by Bristol Meyers Squibb and Glenmark Pharmaceuticals and currently serves on the scientific advisory board of Pionyr Immunotherapeutics. S.L. receives research funding to her institution from Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, Astra Zeneca, and Seattle Genetics; has acted as consultant (not compensated) to Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Eli Lilly, Pfizer, Gilead Therapeutics, and Roche-Genentech; and has acted as consultant (paid to her institution) to Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, Astra Zeneca, Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly, and Bristol Meyers Squibb. S.L. is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. J.M. has served on advisory boards for Bristol-Myers Squibb, Takeda, AstraZeneca, Myovant, Kurome Therapeutics, Kiniksa Pharmaceuticals, Daiichi Sankyo, CRC Oncology, BeiGene, Prelude Therapeutics, TransThera Sciences, and Cytokinetics. J.M. is supported by the NIH (R01HL141466, R01HL155990, R01HL156021, and R01HL160688). J.M. has patents pending related to the treatment of immune-related adverse events including ICI-myocarditis. W.R.S. is a Board or SAB member and holds equity in Ideaya Biosciences, Civetta Therapeutics, Red Ridge Bio, 2Seventy Bio, and Scorpion Therapeutics; has consulted for Array, Astex, Epidarex Capital, Ipsen, Merck Pharmaceuticals, Pierre Fabre, Sanofi, Servier, and Syndax Pharmaceuticals; and receives research funding from Pfizer, Merck, Bristol-Myers, Boehringer-Ingelheim, Ideaya Biosciences, Calico Biosciences, and Ridgeline Discovery. W.R.S. is a co-patent holder on EGFR mutation diagnostic patents. J.S. is an employee of Pfizer, Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Proteins are essential agents of biological processes. To date, large-scale profiling of cell line collections including the Cancer Cell Line Encyclopedia (CCLE) has focused primarily on genetic information whereas deep interrogation of the proteome has remained out of reach. Here, we expand the CCLE through quantitative profiling of thousands of proteins by mass spectrometry across 375 cell lines from diverse lineages to reveal information undiscovered by DNA and RNA methods. We observe unexpected correlations within and between pathways that are largely absent from RNA. An analysis of microsatellite instable (MSI) cell lines reveals the dysregulation of specific protein complexes associated with surveillance of mutation and translation. These and other protein complexes were associated with sensitivity to knockdown of several different genes. These data in conjunction with the wider CCLE are a broad resource to explore cellular behavior and facilitate cancer research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In the era of next-generation sequencing, there are significant challenges to harnessing cancer genome information to develop novel therapies. Key research thrusts in both academia and industry will speed this transition, and lessons learned for cancer will more broadly shape the process for genetic contributions to the therapy of disease more broadly., (Copyright © 2011 Elsevier Inc. All rights reserved.)

An expression vector was modified to permit the rapid synthesis of purified, 32P-labeled, glutathione S-transferase (GST)-retinoblastoma (RB) fusion proteins. The products were used to screen lambda gt11 expression libraries, from which we cloned a cDNA encoding a polypeptide (RBAP-1) capable of binding directly to a putative functional domain (the pocket) of the retinoblastoma gene product (RB). The RB "pocket" is known to bind, directly or indirectly, to the cellular transcription factor, E2F, implicated in cell growth control. We have found that RBAP-1 copurifies with E2F, interacts specifically with the adenovirus E4 ORF 6/7 protein, binds specifically and directly to a known E2F DNA recognition sequence, and contains a functional tranasactivation domain. Therefore, RBAP-1 is a species of E2F and can bind specifically to the RB pocket.