Twentieth Anniversary of Molecular Cancer Therapeutics: A Vision for the Future.

Abstract

The year 2021 marks the 20th anniversary of Molecular Cancer Therapeutics (MCT). This landmark is a good time for the journal to reflect on its past contributions and look forward to its continuing mission to impact patients. MCT was launched with the November 2001 issue under the stellar talents of its Founding Editor-in-Chief, Daniel D. Von Hoff, to help accelerate the exchange of important information in the development of new therapeutic and preventive agents. Not coincidentally, 2001 was a landmark year for cancer therapeutics: imatinib, a small-molecule kinase inhibitor of BCR/Abl, was approved by the FDA for the treatment of Ph+ leukemias, ushering in a remarkably productive period in medicinal chemistry. This period ultimately resulted in the current group of 52 FDA-approved selective small-molecule kinase inhibitors, 46 of which are used to treat cancer, and some of which are curative or nearly curative in the treatment of their target diseases. One year before imatinib, the FDA also approved the first antibody–drug conjugate, Mylotarg. There are now 10 FDA-approved antibody–drug conjugates and many more in early- and late-stage clinical trials, each targeting specific tumor-associated proteins. These stunning achievements produced a sea-change in thinking about cancer, resulting in a clear path for drug hunters to use genomics data to develop specific drugs for specific cancers. We are no longer searching for the cure for lung cancer: because every tumor is unique, we need selective therapies for each one.The great creativity and ingenuity of the scientific community continues to expand the repertoire of therapeutic designs and strategies. Bispecific antibodies and T-cell engagers (BiTE), proteolysis targeting chimeras, antibody cytokine fusions, miRNAs, long noncoding RNAs, RNAis, cell therapies, gene therapies, radio-immunotherapeutics, and many more represent selective therapeutics directed toward specific cancers. To reflect this constant evolution of the therapeutics field in the mission of MCT, our editorial board includes experts in chemistry, protein-based therapeutics, immunotherapy, radiation, oncolytic vaccines, and cellular therapy. MCT is honored that Dr. Razelle Kurzrock has taken on the special role of Reviews Editor. Dr. Joel Morris has graciously taken on the special role of chemistry reviewer. Drs. Paul Workman, Susan M. Galbraith, Louis F. Stancato, John Lazo, and Martine F. Roussel have had long-distinguished careers in drug discovery and development with a focus on the clinical translation of inhibitors of DNA repair, cyclin-dependent kinases (CDK), checkpoint kinases (CHK), HSPs, hedgehog pathway, and protein tyrosine phosphatases. These senior editors are also experienced in the application of big data to drug discovery. Drs. Yibin Kang, Timothy P. Cripe, and Marco Ruella bring expertise in immunomodulatory drugs, proteasome inhibitors, antibodies, checkpoint inhibitors, oncolytic vaccines, CAR T cells, and drug mechanisms of action. Dr. Akash Patnaik is an expert in preclinical models, especially immunocompetent preclinical mouse models, and Dr. Seth M. Pollack brings expertise in preclinical models and early clinical trials to explore specific drug sensitivity of individual tumors. Drs. Peter D. Senter, Puja Sapra, and Iqbal Grewal give MCT deep expertise in antibody–drug conjugates, bispecific antibodies, antiangiogenic agents, BiTEs, immune checkpoint inhibitors, and agents targeting mutant oncogenes. Drs. Peter Houghton and Ricky Johnstone have deep expertise in preclinical drug development and agents that target oncogenic drivers directly, apoptosis regulators including MCL-1, BCL-2, and CDK9, and the potential for combining agents that target the tumor microenvironment and immune-directed therapies. Dr. Candace Johnson has expertise in metabolic features and metabolic relationships with response to targeted agents. Dr. Brion W. Murray has expertise in RNA, spliceosome processes, arginine demethylation, and other RNA-related processes. Dr. David Kirsch is an expert in radiobiology and combining radiation with targeted agents, including inhibitors of the DDR kinases DNA-dependent protein kinase, ataxia telangiectasia mutated, ataxia telangiectasia related (ATR), and immune or cell-cycle checkpoint inhibitors as well as radiopharmaceuticals. Dr. Dario Neri is an expert in biopharmaceuticals including antibody–cytokine fusion proteins, cytokine engineering, and combination strategies.MCT plans to utilize this diverse editorial experience in the coming years to streamline experimental therapeutics into their clinical study. The First Disclosure article type allows rapid dissemination of new drug candidates and was the first step in achieving this goal. While continuing its tradition of publishing influential small-molecule and engineered antibody studies, this new team will inject expertise in fields such as cell-based therapies, gene therapies, and vaccines to reflect the transformation that has occurred in the field of cancer experimental therapeutics. Relying on its stature, impact, and respect among cancer researchers interested in therapeutics, the journal will drive the narrative of drug translation to achieve Dr. Von Hoff's and the AACR's vision of impacting the patient.