Single-cell sequencing is used to investigate tumor evolution. Bulk tumor DNA and RNA sequencing approaches are limited to providing a mixed signal that represents many cancer cell clones and different cell types in the tumor microenvironment. The development of single-cell sequencing to analyze genetic and transcriptional alterations in individual cells from the same cancer provided insights into intratumoral heterogeneity and cancer evolution. (265)
Organoids derived from human tissue are described. In 2009 researchers described how a single small intestinal stem cell could expand to crypt-villus organoids in culture without a mesenchymal niche. In 2011 this work was extended to describe how to generate organoids from mouse colon and human small intestine and colon. (266)
AACR publishes the first issue of the journal, Cancer Discovery.
Novel technique for adoptive T-cell transfer leads to complete responses in two patients with chronic lymphocytic leukemia. Genetically engineered T cells expressing chimeric antigen receptors that target CD19 and contain a costimulatory domain from CD137 and the T-cell receptor zeta chain display potent activity in vivo. (267,268)
Ruxolitinib (Jakafi), the first drug to treat myelofibrosis and first-in-class JAK1 and 2 inhibitor, is approved. This was the first FDA approval supported by patient reported outcomes. Myelofibrosis is associated with dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Ruxolitinib inhibits JAK1 and 2. (269)
FDA approves crizotinib (Xalkori) to treat ALK-positive NSCLC. FDA granted accelerated approval for crizotinib to treat locally advanced or metastatic NSCLC patients with tumors that were positive for ALK rearrangements. ALK-positive tumors are identified with an FDA-approved test. Full FDA approval was granted in 2013, just six years after the identification of mutant ALK fusion transcripts in a subset of NSCLC patients. (270)
BRAF inhibitor vemurafenib (Zelboraf) and its companion diagnostic are approved by FDA to treat melanoma tumors expressing the BRAF V600E mutation. BRAF is mutated in approximately half of those with late-stage melanoma. Vemurafenib was approved with its companion diagnostic test, cobas 4800 BRAF V600 Mutation Test, which is used to determine whether a patient’s tumor expresses the BRAF V600E mutation. (271)
Long noncoding RNAs emerge as critical regulators of cancer biology. The identification of abundant long noncoding RNAs (lncRNAs) in humans catalyzed the characterization of their role in cancer. Tumor suppressive and oncogenic functions of lncRNAs have been described across cancer types. (272)
Abiraterone acetate (Zytiga), which decreases androgen production, is approved for metastatic, castration-resistant prostate cancer. Abiraterone acetate targets cytochrome P450 17A1 (CYP17A1) to inhibit androgen production from the testes, adrenal glands, and tumor. (273)
Ipilimumab (Yervoy), a monoclonal antibody inhibiting the checkpoint protein CTLA-4, is approved for advanced melanoma. Ipilimumab is the first FDA-approved immune checkpoint inhibitor. (274)
Brentuximab vedotin (Adcetris), the first new drug to treat Hodgkin lymphoma in over 30 years and the first specifically indicated to treat systemic anaplastic large cell lymphoma, is approved. Because brentuximab–vedotin is an antibody-drug conjugate, the antibody is able to direct the drug to CD30, a cell membrane protein expressed on lymphoma cells. (275)
Regular aspirin use may reduce the risk of several cancers and distant metastases. Although several important questions need to be answered before aspirin can be considered for use for cancer prevention, studies suggest that aspirin use may reduce both long-term risk of cancer death and short-term cancer incidence and mortality. (276,277)
AACR publishes its first annual Cancer Progress Report, a comprehensive educational document for both Congress and the public that chronicles the progress of cancer research and serves as a call to action in the fight against cancer.
It is discovered that CRISPR-Cas9 is RNA-guided DNA endonuclease. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems were originally identified in some bacteria and archaea and conferred adaptive immunity against viruses and plasmids. After the components of the system were identified, the mechanism was studied in vitro. The CRISPR-Cas9 system is a family of endonucleases that use dual-RNAs for site-specific DNA cleavage. These papers describe “the potential to exploit the system for RNA-programmable genome editing.” (278,279)
NIH Human Microbiome Project defines the normal microbial makeup of healthy humans. NIH launched the Human Microbiome Project in 2007 to characterize the human microbiota and analyze their role in health and disease. In 2012 a consortium of researchers published a series of coordinated reports, creating the first reference data for the normal human microbiome.
Major checkpoint inhibitor shows dramatic clinical trial results. An anti-PD-1 monoclonal antibody drastically shrank tumors in patients with melanoma, kidney cancer, and advanced NSCLC. (280)
Breakthrough Therapy designation is established for FDA. This designation expedites the development and review of drugs that treat a serious or life-threatening disease or condition and provide substantial improvement over existing therapies.
Number of cancer survivors reaches an all-time high of 13.7 million.
Vismodegib (Erivedge) is the first drug approved for basal cell carcinoma, the most common type of skin cancer. Vismodegib inhibits the Hedgehog pathway. Of patients with metastatic disease who received vismodegib, 30% experienced a partial response; of those with locally advanced disease, 43% experienced a complete or partial response. (281)
Whole-genome sequencing explains exceptional response to therapy in a single patient. Massively parallel sequencing (MPS) was used to provide biologic insights and identify the molecular pathology of prostate tumors. Deep RNA and shallow DNA sequencing was performed in primary tumors and matched metastases in six patients. The results provided a foundation for developing MPS-based molecular pathology. (282)
Functional consequences of intratumoral heterogeneity are described, suggesting the limitations of single tumor-biopsy samples. Multiple, spatially separated tissue samples were obtained from primary renal carcinomas and associated metastatic sites. Exome sequencing, chromosome aberration analysis, and ploidy profiling were performed. Gene expression, immunohistochemistry, and mutation functional analysis further characterized the tissue samples. Roughly 63 to 69% of all somatic mutations were not detectable across every regional sample from the same tumor. Gene expression signatures varied in different regions of the tumor. This heterogeneity across the same tumor presents challenges when using a single tumor biopsy and provides further evidence of the Darwinian selection of cell populations within a tumor that can lead to therapeutic resistance. (283)
AACR-Pancreatic Cancer Action Network Think Tank, “The 2020 Goal for Pancreatic Cancer: Driving the Agenda Forward,” is held.
AACR Cancer Epigenome Think Tank is held.
2013
The term “financial toxicity” is coined. Financial toxicity is recognized as a potential adverse event in cancer treatment. Out-of-pocket costs related to cancer treatment can impede delivery of high-quality care and diminish quality of life. Both objective financial burden and subjective financial distress are components of financial toxicity. (284,285)
CAR T-cell therapy achieves complete responses in acute lymphoblastic leukemia. Two separate studies, both with T cells engineered to express chimeric antigen receptor targeting CD19 on leukemic B cells, saw dramatic results in adults and children with relapsed and refractory B-ALL. (286,287)
Radium Ra 223 dichloride (Xofigo), which can bind with minerals in the bone and deliver radiation directly to bone tumors, is approved by FDA to treat metastatic, castration-resistant prostate cancer that has spread to bones. This is the first FDA-approved alpha-emitting radionuclide. Because radium Ra 223 dichloride delivers radiation directly to bone tumors, it limits the damage to the surrounding normal tissues. (288)
CRISPR-Cas9 is adapted for genome editing in eukaryotic cells. This study engineered two different type II CRISPR/Cas systems to show that Cas9 nucleases, directed by short RNAs, can facilitate site-specific cleavage in genomic loci of human and murine cells. (289)
Microbiome helps to stimulate anticancer immune responses. Resident gut bacteria have the potential to move from the intestines to lymphoid tissues such as the spleen and lymph nodes; once there, they stimulate T-cell responses that aid antitumor response. (290,291)
T-DM1 is approved for late-stage HER2-positive breast cancer. Ado-trastuzumab emtansine (T-DM1; Kadcyla) was approved to treat patients who were previously treated with the anti-HER2 therapy trastuzumab and taxanes, a class of chemotherapy drugs commonly used for the treatment of breast cancer. T-DM1 is an antibody-drug conjugate, in which the antibody trastuzumab is connected to the drug DM1 that interferes with cancer cell growth. T-DM1 delivers the drug to the cancer site to shrink the tumor. (292)
AACR partners with over 200 organizations and institutions to conduct the first Rally for Medical Research in support of increased funding for biomedical research, April 8, Washington, DC. About 10,000 people attended the Rally, which was held outside the Washington, DC, convention center at the time of AACR Annual Meeting 2013.
Inaugural AACR-CRI Lloyd J. Old Award in Cancer Immunology is presented to James P. Allison.
Daniel S. Chen and Ira Mellman publish their seminal paper, “Oncology meets immunology: the cancer-immunity cycle.” In the paper, Chen and Mellman described a series of seven steps by which the immune system recognizes and kills cancer cells. This iterative cycle provides the intellectual foundation for the development of cancer immunotherapeutics. (293)
AACR holds its first Special Conference focused on pediatric cancer, “Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes.”
AACR launches Task Forces on Radiation Oncology and Surgical Oncology.
2014
NCI National Clinical Trials Network (NCTN) is formed. NCTN was established to provide an integrated clinical trials program to take advantage of scientific advances in our knowledge of tumor biology and targeted therapies. These scientific advances created a need for cancer clinical trials with the capacity to screen large numbers of patients in order to identify those whose tumors contained distinct molecular targets.
Liquid biopsy allows for noninvasive screening for early detection of cancers. Liquid biopsy is a screening of patient blood, which is a less invasive means to detect circulating tumor DNA shed by cancer cells that can serve as a biomarker for cancer at earlier stages, when there is better potential for survival. Dying cancer cells shed their DNA into the bloodstream even at very early stages; routine screening has the potential to detect cancer earlier, before the cancer has advanced to late stages when treatment is less effective. A liquid biopsy can also monitor a patient’s response to treatment and begin to help researchers understand why certain cancers become resistant to treatment. (294)
Blinatumomab (Blincyto) is the first bispecific T-cell engager (BiTE) approved by the FDA. Blinatumomab (Blincyto) engages the body’s T cells against Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL. In earlier clinical studies, 32% of participants showed complete remission for approximately 6.7 months. (295)
NCI launches the Exceptional Responders Initiative. The goal of this study is to understand the exceptional treatment responses of those cancer patients who respond to treatments that are not effective for most other patients.
FDA approves first immunotherapy targeting the checkpoint protein PD-1. Pembrolizumab (Keytruda) became the first PD-1-targeting immune checkpoint inhibitor approved by FDA. The accelerated approval was for using pembrolizumab to treat certain patients with melanoma. (296)
FDA approves olaparib (Lynparza) for advanced ovarian cancer along with a laboratory-developed test companion diagnostic to identify appropriate patients through the detection of the presence of mutations in BRCA genes in blood samples. Olaparib was the first FDA-approved therapeutic that inhibits PARP and was approved with the genetic test, BRACAnalysis CDx, a companion diagnostic. BRACAnalysis CDx detects mutations in BRCA1 and BRCA2 genes (gBRCAm) in blood samples from patients and can guide treatment decisions for the use of olaparib. (297)
Combination immunotherapy delivers dramatic results. Combination nivolumab (anti-PD-1) and ipilimumab (Yervoy; anti-CTLA-4), both immune checkpoint inhibitors, in a phase Ib clinical trial saw 90% response rates in patients with advanced melanoma.
AACR opens its first two international satellite offices in Shanghai, China, and Toronto, Ontario, Canada.
AACR membership passes 35,000.
AACR holds two Think Tanks, “Future of Pediatric Cancer Research and Care,” and “Charting the Future of Cancer Disparities Research” (the latter jointly with American Cancer Society, ASCO, and NCI).
FDA approves Gardasil 9 for the prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV16, 18, 31, 33, 45, 52, and 58. FDA’s decision was based on a clinical trial that showed Gardasil 9 was effective at preventing precancerous abnormalities that precede invasive cervical, vulvar, and vaginal cancers caused by HPV31, 33, 45, 52, and 58. (298)
2015
Joint policy statement calling for the regulation of Electronic Nicotine Delivery Systems (ENDS) is released by AACR and ASCO. (299)
NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trials open for enrollment. This phase II precision medicine trial explores treating patients based on the molecular profiles of their tumors regardless of cancer type.
First oncolytic virus therapy, talimogene laherparepvec (T-VEC, trade name Imlygic), is approved by FDA for treating certain patients with melanoma. T-VEC is a herpes simplex virus type 1 that has been genetically modified so that it is less able to cause disease, is more selective for killing cancer cells, and is more likely to promote an anticancer immune response. FDA approved T-VEC for the treatment of melanoma lesions in the skin and lymph nodes that cannot be removed completely by surgery. (300)
Daratumumab (Darzalex) is the first monoclonal antibody approved for the treatment of multiple myeloma. In clinical studies, 29-36% of patients experienced a complete or partial reduction in their tumor burden. (301)
Precision Medicine Initiative is announced. The Precision Medicine Initiative leverages advances in genomics, methods for managing and analyzing large data sets, and health information technology to accelerate biomedical discoveries and bring precision medicine to many aspects of health care, including cancer.
Mutation signatures of in vitro carcinogen exposure are extracted from mammalian genome. Mutational processes leave characteristic marks on the genome, creating a record of the mutagenic processes that occur throughout the life of an organism. Earlier research linked exposure to environmental carcinogens to mutations in a specific gene, such as p53. With the advent of massively parallel next-generation sequencing technology, these signatures can now be extracted from the sequences of whole genomes or all protein-coding exons, allowing greater precision in characterizing the mutational signature than can be obtained from analysis of a single gene. This opens up the possibility of identifying mutational signatures in the genome associated with exposures that contribute to the burden of human cancer. A portion of this work was published in the AACR journal Cancer Research. (302,303)
FDA approves osimertinib (Tagrisso) to treat EGFR T790M mutation-positive NSCLC. FDA granted accelerated approval for osimertinib (Tagrisso) to treat patients whose tumors have a specific EGFR mutation (T790M) and whose disease has gotten worse after treatment with other EGFR-blocking therapy. (304)
Percentage of adults in the U.S. who smoke declines from 21% in 2005 to 15% in 2015. (305)
First cyclin-dependent kinase inhibitor is approved for cancer treatment. Palbociclib (Ibrance) is the first cyclin-dependent kinase 4/6 inhibitor approved by FDA. Palbociclib was approved for postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Adding palbociclib to letrozole doubled the median progression-free survival from 10 to 20 months. (306)
AACR announces the launch of AACR Project GENIE (Genomics Evidence Neoplasia Information Exchange). AACR Project GENIE is an international data-sharing project that aggregates and links clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients.
Vice President Biden announces that he will forgo a run for the U.S. presidency to dedicate his energy to “a moonshot in this country to cure cancer…an absolute national commitment to end cancer as we know it today.” In a statement, AACR CEO Margaret Foti, PhD, MD (hc), noted that “the vice president is absolutely correct: We are at a turning point in cancer research, … [but] future progress for cancer patients will require more research and more funding for the federal agencies that are vital for fueling progress against cancer, in particular, the NIH, NCI, and FDA.”
AACR Radiation Oncology Think Tank, “Optimizing Cancer Care through Advancements in Radiation Science and Medicine,” is held.
2016
On January 8, a group of 15 AACR leaders meets with Vice President Biden’s senior staff to discuss the state of cancer research and the vice president’s commitment to a national initiative to eliminate cancer. Four days later, during the State of the Union Address, President Obama announced the launch of a “new national effort” to eliminate cancer to be led by the vice president.
AACR Cancer Prevention Summit, “Shaping the Future of Cancer Prevention: A Roadmap for Integrative Cancer Science and Public Health,” is held.
Vice President Biden addresses attendees of AACR Annual Meeting 2016. The vice president thanked the assembled researchers for devoting their lives to cancer research and encouraged them to share their ideas to accelerate progress against cancer.
AACR celebrates its publishing centennial, commemorating the 100th anniversary of the publication of its first journal, The Journal of Cancer Research, and the 75th anniversary of the publication of its oldest continuously published journal, Cancer Research.
NCI-Match Trials interim analysis is released at AACR Annual Meeting.
Composition of the metastatic tumor microenvironment is revealed at the single-cell level. Single-cell analysis of metastatic melanoma samples characterized the complex tumor ecosystem, revealing distinct microenvironmental patterns, cell states, and cell–cell interactions. (307)
FDA approves first immunotherapy targeting the protein PD-L1. Atezolizumab (Tecentriq) became the first PD-L1-targeting immune checkpoint inhibitor approved by FDA. The accelerated approval was for treatment of certain patients with locally advanced or metastatic bladder cancer. (308)
FDA approves the first liquid biopsy test. FDA approved a liquid biopsy test, a companion diagnostic test called cobas EGFR Mutation Test v2. The test uses plasma samples to identify patients with metastatic NSCLC eligible for treatment with the EGFR-targeted therapeutic erlotinib (Tarceva). The need for this noninvasive test is particularly important in cases in which a tumor biopsy is not possible. (309)
E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General is released.
First drug to target the Bcl-2 protein is approved. Venclexta (venetoclax), also known as ABT-199, was the first FDA-approved drug that targets the Bcl-2 protein and interferes with the ability of cancer cells to evade apoptosis. Venclexta was approved for the treatment of patients with chronic lymphocytic leukemia and a 17p deletion. Phase II trials demonstrated an overall response rate of 80%. (310)
AACR Think Tank on Genomics in Clinical Medicine is held.
NCI’s Genomic Data Commons is launched. The Genomic Data Commons is a data-sharing platform that provides the cancer research community with a unified data repository supporting cancer genomic studies. NCI-generated data from some of the largest and most comprehensive cancer genomic datasets as well as datasets from organizations are harmonized, allowing data from various sources to be compared directly.
AACR holds two Workshops, “Childhood Cancer Predisposition, Optimizing Pediatric Surveillance and Care through Precision Genetics,” and “Liquid Biopsies in Oncology Drug and Device Development” (the latter jointly with FDA).
Cancer Moonshot Blue Ribbon Panel report is released and details 10 research recommendations for achieving the goals of the Cancer Moonshot to make a decade’s worth of progress in five years.
21st Century Cures Act is passed, including $18 billion in supplemental funding over seven years to fund Cancer Moonshot projects and initiatives.
2017
FDA launches the Oncology Center of Excellence, making oncology the first disease area to have a coordinated review of drugs, biologics, and devices across the agency’s three medical product centers.
AACR announces the first public release of data aggregated through its Project GENIE initiative, consisting of nearly 19,000 de-identified genomic records and limited clinical data. By aggregating the historical and ongoing clinical sequencing efforts from leading international institutions, AACR Project GENIE has formed a real-world registry of cancer data that will continue to grow with time. These data are being used to answer important clinical questions, and will be a community resource that will undoubtedly catalyze numerous new research projects.
NCTN/NCORP Data Archive, a new centralized repository of patient-level data from phase III clinical trials, is launched by NCI.
AACR International Conference on New Frontiers in Cancer Research is held in Cape Town, South Africa—the first AACR meeting on the African continent.
Deep convolutional neural network is developed that can classify skin cancer from images. This study reported the development of a deep convolutional neural network that can classify digital images of skin lesions at least as accurately as can board-certified dermatologists. Artificial intelligence (AI) based approaches have the potential to improve the timing and accuracy of cancer diagnosis, leading to better patient outcomes. (311)
iRECIST is developed as a modified guideline for use in cancer immunotherapy trials. The mechanism of action of immunotherapies can lead to distinct patterns of response, limiting the accuracy of traditional response criteria such as Response Evaluation Criteria in Solid Tumors (RECIST). The RECIST Working Group developed a consensus guideline for the use of a modified RECIST, termed iRECIST, to ensure consistent design and data collection in clinical trials evaluating immune-based therapeutics. (312)
FDA approves first molecularly targeted therapeutic for treating acute myeloid leukemia. Midostaurin (Rydat) targets FLT3, which is mutated in about 25% of acute myeloid leukemia (AML) cases. FDA approved this therapeutic for treating FLT3 mutation-positive AML after it was shown to improve survival compared with standard of care. (313)
Inaugural AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research is presented to Roger S. Lo.
FDA grants first approval of an anticancer therapy for treating cancer at any site, as long as the cancer is found to have certain molecular alterations. Prior to this approval, all anticancer treatments were approved for a particular type of cancer. In this milestone case, FDA approved the immunotherapeutic pembrolizumab (Keytruda) for treating certain adults and children with any type of solid tumor characterized by the presence of specific biomarkers, called microsatellite instability-high and DNA mismatch repair deficiency. (314)
Comprehensive guidelines are developed for screening of pediatric patients with cancer predisposition. These consensus screening recommendations impacted the global triaging, tracking, and treatment of children genetically predisposed to cancer. (315)
The AACR International Conference on Translational Cancer Medicine is held in Sáo Paulo, Brazil—the first AACRmeeting on the South American continent.
NCI-COG Pediatric MATCH opens for enrollment. NCI and the Children’s Oncology Group (COG) opened enrollment to Pediatric MATCH (Molecular Analysis for Therapy Choice), a precision medicine cancer treatment trial designed to extend molecular analysis and targeted treatment of cancer to pediatric patients. Pediatric MATCH seeks to determine if treating tumors with molecularly targeted drugs based on the tumor’s genetic characteristics rather than the type of cancer or cancer site will be effective. (316)
FDA approves first inhibitor of nuclear export, selinexor (Xpovio). Selinexor targets a protein called XPO1, which is found at elevated levels in multiple myeloma cells. The accelerated approval of selinexor was granted based on results from a phase II clinical trial that showed that 25% of heavily pretreated patients responded to treatment with the new molecularly targeted therapeutic. (317)
First inhibitor of isocitrate dehydrogenase (IDH) 1 and 2 is approved for cancer treatment. Enasidenib (Idhifa) was the first IDH1 and IDH2 inhibitor approved by FDA. Enasidenib was approved for treating patients with relapsed or refractory acute myeloid leukemia with an IDH2 mutation after it was shown that 19% of patients treated with the molecularly targeted therapeutic in a phase I/II clinical trial had complete remission. (318)
First chimeric antigen receptor (CAR) T-cell therapy is approved by FDA. Tisagenlecleucel (Kymriah) became the first CAR T-cell therapy approved by FDA. The approval was for using tisagenlecleucel to treat children and young adults up to the age of 25 with B-cell acute lymphoblastic leukemia (ALL) that had not responded to standard treatments or had relapsed at least twice. (319)
FDA grants first authorization of a next-generation sequencing-based multigene panel companion diagnostic test (MSK-IMPACT). MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) uses next-generation sequencing to look for mutations in 468 genes and other critical genetic aberrations. By using the test to profile a patient’s cancer, health care providers can gain information that may help inform them as to how best to treat patients. (320)
2018
Microbiome is linked to the response to immune checkpoint blockade therapy. Three studies investigated the relationship between the microbiome and therapeutic response in cancer patients treated with anti-PD-1 immune checkpoint blockade therapy. The composition of the commensal microbiome in the intestines correlated with patient response to PD-1 blockade. Antibiotic treatment suppressed the efficacy of anti-PD-1 therapy while fecal microbiota transplantation from responding patients improved responses in mouse models. (321-323)
First AI-based software is cleared by FDA to analyze medical scans. The Arterys Oncology AI suite uses AI to help radiologists interpret lung CT scans and liver CT and MRI scans. This software allows radiologists to efficiently confirm, evaluate, quantify, and report on the absence or presence of tumors in the lungs and liver. (324)
AACR Pediatric Cancer Working Group launches efforts to serve as a bridge between NCI’s Pediatric Preclinical Testing Consortium and the Pediatric Preclinical Proof-of-Concept Program of the Innovative Therapies for Children with Cancer Consortium to improve both platforms’ efforts to standardize and harmonize.
AACR Pediatric Cancer Working Group spearheads the formation of a working partnership with the ACCELERATE Innovation for Children and Adolescents with Cancer platform to improve pediatric cancer drug development efforts worldwide.
Assay monitoring immune parameters provides information for managing certain patients with colon cancer. Analysis of immune infiltration of stage I–III colon cancers using the Immunoscore assay was shown to reliably estimate risk of disease recurrence in an international study in which 14 centers in 13 countries participated. (325)
AACR partners with the organizers of the International Conference on Malignant Lymphoma (ICML) to bring a version of that meeting to the United States. In June, the Inaugural AACR International Meeting on “Advances in Malignant Lymphoma” was held in Boston.
FDA grants first authorization of a next-generation sequencing-based test to determine whether patients with acute lymphoblastic leukemia or multiple myeloma have very low levels of cancer cells remaining after treatment. The ClonoSEQ assay is a test that includes the use of next-generation sequencing to look for the presence of minimal residual disease (MRD) in the bone marrow of patients with acute lymphoblastic leukemia or multiple myeloma. By using the test to establish whether a patient has MRD, a health care provider can gain information on how well a patient has responded to treatment and how long remission may last. (326)
FDA approves the first molecularly targeted therapeutic for treating any cancer type with a specific genetic alteration. The molecularly targeted therapeutic larotrectinib (Vitrakvi) is approved for treating certain children and adults who have any type of solid tumor that tests positive for a genetic aberration called an NTRK gene fusion, making it both tissue- and age-agnostic. (327)
Childhood Cancer Survivorship, Treatment, Access, and Research (STAR) Act is enacted. The STAR Act expanded opportunities for childhood cancer research by authorizing NCI to support the collection of biospecimens and relevant information from children, adolescents, and young adults with cancer, as well as by utilizing cancer registries to improve tracking of childhood cancer incidence.
“AACR White Paper: Shaping the Future of Cancer Prevention—A Roadmap for Advancing Science and Public Health” is published in Cancer Prevention Research. (328)
Fellows of the AACR Academy establishes a formal governance structure. Judy E. Garber was elected as its first president.
AACR eliminates annual dues for early-career Associate Members who are graduate students, medical students and residents, and postdoctoral and clinical fellows who are enrolled in educational or training programs that could lead to careers in cancer research.
2019
AACR Project GENIE enters into a major research collaboration with a coalition of nine biopharmaceutical companies, known as the Biopharma Collaborative, later expanded to 10, that will accelerate the rate of clinical data collection and advance precision oncology to benefit cancer patients.
Congress passes legislation known as Tobacco 21, which raises the minimum age for tobacco use to 21. In December 2019, the U.S. president signed legislation amending the Federal Food, Drug, and Cosmetic Act. The legislation raised the federal minimum age for sale of tobacco products, including e-cigarettes, from 18 to 21. (329)
Number of cancer survivors in the U.S. reaches 16.9 million. (330,331)
AACR membership passes 45,000.
AACR Women in Cancer Research (WICR), a membership group within AACR, celebrates 20 years. The mission of WICR is to recognize women’s scientific achievements and foster their career development and advancement in cancer research.
AACR partners with Deloitte to support FDA’s Project Renewal. FDA’s Oncology Center of Excellence launched Project Renewal in 2018 with the goal of updating labeling information for long-standing, off-patent oncology drugs by evaluating accumulated scientific evidence from published research literature. To facilitate this opportunity, FDA engaged Deloitte, which partnered with the AACR to seek strategic scientific advice and perspective, enhance the scientific integrity of a repeatable process, and gain insights into the evidence evaluation process.
2020
AACR publishes the first issue of Blood Cancer Discovery, its ninth journal. Blood Cancer Discovery provides a new platform for the dissemination of pace-setting advances generated by blood cancer researchers and physician-scientists.
International pancancer analysis of whole genomes is published. Analysis of the whole genomes of more than 2,600 tumors from 38 different types of cancer by an international team of researchers provided the most comprehensive insight to date into the causal changes that drive cancer phenotypes. (332)
CRISPR-Cas9-modified T cells are used to treat three patients with advanced cancer. After modifying T cells isolated from three patients with advanced cancer using CRISPR-Cas9, researchers reinfused the cells into the patients, finding that they were well tolerated and survived in the patients for several months. (333)
AACR Minorities in Cancer Research (MICR), a membership group within AACR, celebrates 20 years. The mission of MICR is to eradicate cancer disparities, increase the representation of underrepresented minorities in cancer research, and advance the careers of racially and ethnically diverse cancer researchers.
AACR celebrates 35 years of the AACR Minority Scholar in Cancer Research Award program. This program exposes early-career underrepresented minority scientists to groundbreaking cancer science and medicine and provides mentoring, networking, and other professional development opportunities.
AACR holds its first-ever Virtual Annual Meeting, April 27-28 and June 22-24, in response to the global COVID-19 pandemic. More than 74,000 registrants from 127 countries participated in the meeting.
AACR establishes the AACR COVID-19 and Cancer Task Force to evaluate the impact of the pandemic on cancer research and patient care.
FDA approves selpercatinib (Retevmo) to treat lung and thyroid cancers driven by RET gene mutations or fusions. Selpercatinib was granted accelerated approval by FDA for treating RET-fusion positive NSCLC and thyroid cancer, as well as RET-mutant medullary thyroid cancer. (334)
FDA approves capmatinib (Tabrecta) to treat MET mutation-positive NSCLC. Capmatinib was granted accelerated approval by FDA for treating NSCLC that tests positive for a MET mutation that results in exon 14 skipping using a specific FDA-approved test. Such mutations occur in up to 4% of NSCLC cases. (335)
Inaugural AACR-St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research Grant is presented to James R. Downing. The corresponding Inaugural AACR-St. Baldrick’s Foundation Pediatric Cancer Research Fellowship is presented to Jarno Drost. This award program represents a novel approach to driving impactful research and fostering career advancement for the next generation of pediatric cancer researchers by linking an AACR scientific achievement award to a research grant opportunity for an early career investigator.
AACR releases a statement against racial discrimination and inequality and launches the Racial Inequities in Cancer Research Task Force.
Inaugural AACR Award for Outstanding Achievement in Basic Cancer Research is presented to Cigall Kadoch.
Research to Accelerate Cures and Equity (RACE) for Children Act goes into effect. The RACE for Children Act aims to increase testing in children of cancer agents used to treat cancer in adults where there is a shared molecular target.
AACR holds its first conference on “COVID-19 and Cancer,” with NIAID director Anthony S. Fauci as the keynote speaker.
AACR releases Inaugural AACR Cancer Health Disparities Progress Report. The overarching goal of this historic report is to increase public understanding of cancer health disparities and to underscore the vital importance of cancer health disparities research to saving lives.
FDA approves liquid biopsy next-generation sequencing companion diagnostic test for multiple cancers and biomarkers. FoundationOne Liquid CDx test was approved as a companion diagnostic device for multiple additional biomarkers detected in cell-free DNA isolated from plasma specimens. (336)
AACR launches its collaboration with FDA on Project Livin’ Label. Project Livin’ Label is an educational initiative designed to foster broad understanding of specific oncology product labels and to increase awareness of recent FDA approvals of oncology drugs among physicians, cancer patients and survivors, industry representatives, and other health care professionals.
Incidence of cervical cancer is shown to be substantially reduced by HPV vaccination. In a large study of Swedish women who received HPV vaccination between 2006 and 2017, the incidence of cervical cancer was substantially reduced, with the greatest risk reduction observed in women vaccinated prior to age 17. (337)
FDA and AACR establish Oncology Educational Fellowship. An FDA-AACR Oncology Educational Fellowship began in 2020 to allow early-stage researchers the opportunity to participate in educational sessions with FDA staff on numerous topics, such as investigational new drugs (INDs), expedited approval pathways, dosing requirements, and clinical trial designs.
2021
Data are published reporting that the largest recorded single-year drop (2.4%) in the age-adjusted overall U.S. cancer death rate occurred between 2017 and 2018. (338)
AACR launches Task Forces on Precision Combination Therapy; Exploratory IND/Phase 0 Clinical Trials; and Aging, Stress, and Cancer.
AACR hosts its first Special Conference dedicated exclusively to radiation science and medicine.
FDA approves first B-cell maturation antigen (BMCA)-targeted CAR T-cell therapy for multiple myeloma. Idecabtagene vicleucel (Abecma), which targets a protein present at high levels in multiple myeloma cells (BCMA), was approved by FDA after it was shown to shrink tumors partially or completely in 72% of patients treated. (339)
Cancer Discovery marks its 10th anniversary with publication of a special issue and the launch of the Cancer Discovery Symposium. (340)
Inaugural AACR Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research is presented to Daniel D. Von Hoff.
Inaugural Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of Ruth Bader Ginsburg, is presented to Dannielle Engle.
Inaugural Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of John Robert Lewis, is presented to Avery D. Posey.
First KRAS inhibitor is approved by FDA. Sotorasib (Lumakras) is the first inhibitor of KRAS, which had long been thought to be undruggable. Sotorasib was granted accelerated FDA approval for treating adults who have locally advanced or metastatic NSCLC that harbors a KRAS G12C mutation. The approval was based on results of a phase II clinical trial that showed that treatment with sotorasib shrank tumors in more than 37% of NSCLC patients who had responded poorly to previous treatment with either chemotherapy or immunotherapy. (341)
AACR’s Oncology Development Fund issues its first Request for Proposals. This fund was created with the overarching goal of accelerating breakthrough innovations in cancer prevention, interception, treatment, or cures by investing in oncology-focused investment funds. Investments should have the potential to be superior to standard-of care treatment at the time of market introduction and should lead to benefits for patients.
AACR forms the Cancer Evolution Working Group and the Cancer Prevention Working Group.
FDA approves first hypoxia-inducible factor-2α inhibitor for treatment of cancer. Belzutifan (Welireg) is the first inhibitor of hypoxiainducible factor-2α to be approved by FDA. It is approved for treating adults who have von Hippel- Lindau disease-associated renal cell carcinomas, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgery. (342)
AACR launches its first open access journal, Cancer Research Communications.
Inaugural AACR Career Development Award to Further Diversity, Equity, and Inclusion in Cancer Research and Inaugural AACR Career Development Award to Further Diversity, Equity, and Inclusion in Clinical Cancer Research are launched.
AACR presents the first Bristol Myers Squibb Foundation (BMSF)-American Association for Cancer Research (AACR) Design and Implementation of Clinical Trials Workshop. The workshop, part of a broader BMSF initiative in collaboration with National Medical Fellowships and AACR to increase diversity in clinical trials, introduced principles of clinical trial design/implementation and community engagement, and addressed the challenges involved with clinical research in oncology, hematology, autoimmune disease, and cardiovascular disease.
AACR leads cancer community efforts to prioritize patients with cancer and their household members for COVID-19 vaccinations.
President Biden calls for the establishment of an Advanced Research Projects Agency for Health (ARPA-H) to fund high-risk, high-reward initiatives to deliver biomedical breakthroughs for several diseases including cancer.
Fiftieth anniversary of the National Cancer Act is commemorated.
2022
Data are published reporting a 32% decline in the overall U.S. cancer death rate between 1991 and 2019, driven largely by reductions in deaths from lung cancer and melanoma, a result of improved treatments and national prevention efforts. (343-345)
First T-cell receptor–based anticancer therapeutic is approved by FDA for treating metastatic uveal melanoma.
Tebentafusp-tebn (Kimmtrak) is a bispecific fusion protein comprised of a soluble T-cell receptor fused to an anti-CD3 immune-activating component. Tebentafusp-tebn is not only the first FDA-approved T-cell receptor-based therapeutic, but is also the first FDA-approved therapeutic for the treatment of unresectable or metastatic uveal melanoma. (346)
AACR establishes Trust in Science Task Force.
AACR membership passes 50,000.
AACR celebrates 25 years of the AACR Undergraduate Scholar in Cancer Research Award program.
This program was established to inspire young science students to enter the field of cancer research and provides a unique educational opportunity in support of the development of their careers in science.
AACR COVID-19 and Cancer Task Force releases AACR Report on the Impact of COVID-19 on Cancer Research and Patient Care. The report provided a comprehensive view of the burden of COVID-19 among patients with cancer, the challenges presented by the pandemic to cancer research and patient care, and the changes implemented during the pandemic that have unexpectedly improved research practices and access to care.
President Biden reignites the Cancer Moonshot initiative to end cancer as we know it. The initiative set two ambitious goals: to reduce the death rate from cancer by at least 50% over the next 25 years and to improve the experience of people and their families living with and surviving cancer.
AACR holds its first Special Conference on “Evolutionary Dynamics in Carcinogenesis and Response to Therapy.”
Inaugural AACR Award for Outstanding Achievement in Blood Cancer Research is presented to John E. Dick.
Inaugural AACR James S. Ewing-Thelma B. Dunn Award for Outstanding Achievement in Pathology in Cancer Research is presented to Elaine S. Jaffe.
Inaugural Victoria’s Secret Global Fund for Women’s Cancers Meritorious Awards, in Partnership with Pelotonia and AACR, are presented to Joan S. Brugge, Susan M. Domchek, Karen H. Lu, Lisa A. Newman, and Martine J. Piccart.
AACR celebrates the 115th anniversary of its inception.
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