KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?

Cancer statistics, 2022

(2022) Rebecca L. Siegel et al.   CA-A CANCER JOURNAL FOR CLINICIANS

Drugging the Next Undruggable KRAS Allele-Gly12Asp

(2022) Qinheng Zheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge

(2022) Zhongwei Mao et al.   Cell Discovery

Discovery of Thieno[2,3-d]pyrimidine-based KRAS G12D inhibitors as potential anticancer agents via combinatorial virtual screening

(2022) Ling Li et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer

(2022) Rom Leidner et al.   NEW ENGLAND JOURNAL OF MEDICINE

Expanding the Arsenal of Clinically Active KRAS G12C Inhibitors

(2022) Kathryn C. Arbour et al.   JOURNAL OF CLINICAL ONCOLOGY

Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S)

(2022) Ziyang Zhang et al.   Nature Chemical Biology

Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation

(2022) Pasi A. Jänne et al.   NEW ENGLAND JOURNAL OF MEDICINE

KRAS ‐G12D mutation drives immune suppression and the primary resistance of anti‐PD‐1/PD‐L1 immunotherapy in non‐small cell lung cancer

(2022) Chengming Liu et al.   Cancer Communications

Chemoselective Covalent Modification of K-Ras(G12R) with a Small Molecule Electrophile

(2022) Ziyang Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeting KRAS in pancreatic cancer: new drugs on the horizon

(2021) Sahar F. Bannoura et al.   CANCER AND METASTASIS REVIEWS

The KRAS-G12C inhibitor: activity and resistance

(2021) Jiao Liu et al.   CANCER GENE THERAPY

Acquired Resistance to KRASG12C Inhibition in Cancer

(2021) Mark M. Awad et al.   NEW ENGLAND JOURNAL OF MEDICINE

Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting

(2021) Adham S. Bear et al.   Nature Communications

KRAS Inhibitors– yes but what next? Direct targeting of KRAS– vaccines, adoptive T cell therapy and beyond

(2021) Misako Nagasaka et al.   CANCER TREATMENT REVIEWS

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC

(2021) Erica C. Nakajima et al.   CLINICAL CANCER RESEARCH

Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor

(2021) Xiaolun Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition

(2020) Jenny Y. Xue et al.   NATURE

Oncogenic Kras driven metabolic reprogramming in pancreas cancer cells utilizes cytokines from the tumor microenvironment

(2020) Prasenjit Dey et al.   Cancer Discovery

Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research

(2020) Zhidong Wang et al.   Frontiers in Immunology

RAS-targeted therapies: is the undruggable drugged?

(2020) Amanda R. Moore et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting Mutant KRAS in Pancreatic Cancer: Futile or Promising?

(2020) Friederike Inga Nollmann et al.   Biomedicines

Regulation and modulation of antitumor immunity in pancreatic cancer

(2020) Joshua Leinwand et al.   NATURE IMMUNOLOGY

KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors

(2020) David S. Hong et al.   NEW ENGLAND JOURNAL OF MEDICINE

Memory T cells targeting oncogenic mutations detected in peripheral blood of epithelial cancer patients

(2019) Gal Cafri et al.   Nature Communications

Durvalumab With or Without Tremelimumab for Patients With Metastatic Pancreatic Ductal Adenocarcinoma

(2019) Eileen M. O’Reilly et al.   JAMA Oncology

The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity

(2019) Jude Canon et al.   NATURE

Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study

(2019) Suneel D. Kamath et al.   ONCOLOGIST

The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

(2019) Jill Hallin et al.   Cancer Discovery

Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors

(2019) Brian A. Lanman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pancreatic cancer subtypes: a roadmap for precision medicine

(2018) Carolina Torres et al.   ANNALS OF MEDICINE

Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

(2018) Matthew R. Janes et al.   CELL

Effect of mutant variants of the KRAS gene on PD-L1 expression and on the immune microenvironment and association with clinical outcome in lung adenocarcinoma patients

(2018) Alexander T. Falk et al.   LUNG CANCER

Harnessing the Immune System in Pancreatic Cancer

(2018) Satya Das et al.   CURRENT TREATMENT OPTIONS IN ONCOLOGY

Targeting the α4–α5 dimerization interface of K-RAS inhibits tumor formation in vivo

(2018) Imran Khan et al.   ONCOGENE

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

(2017) Dung T. Le et al.   SCIENCE

Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation

(2016) Christopher J. Tape et al.   CELL

RAS isoforms and mutations in cancer at a glance

(2016) G. Aaron Hobbs et al.   JOURNAL OF CELL SCIENCE

Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design

(2016) Jonathan M. L. Ostrem et al.   NATURE REVIEWS DRUG DISCOVERY

T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer

(2016) Eric Tran et al.   NEW ENGLAND JOURNAL OF MEDICINE

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

(2016) P. Lito et al.   SCIENCE

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State

(2016) M. P. Patricelli et al.   Cancer Discovery

Ras activation revisited: role of GEF and GAP systems

(2015) Anne Hennig et al.   BIOLOGICAL CHEMISTRY

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

(2015) J. C. Hunter et al.   MOLECULAR CANCER RESEARCH

Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors

(2015) Q. J. Wang et al.   Cancer Immunology Research

Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia

(2014) Florencia McAllister et al.   CANCER CELL

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

(2013) Jonathan M. Ostrem et al.   NATURE

Oncogenic Kras-Induced GM-CSF Production Promotes the Development of Pancreatic Neoplasia

(2012) Yuliya Pylayeva-Gupta et al.   CANCER CELL

The Pancreas Cancer Microenvironment

(2012) C. Feig et al.   CLINICAL CANCER RESEARCH

Presence of Somatic Mutations in Most Early-Stage Pancreatic Intraepithelial Neoplasia

(2012) Mitsuro Kanda et al.   GASTROENTEROLOGY

Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice

(2012) Meredith A. Collins et al.   JOURNAL OF CLINICAL INVESTIGATION

Phase 2 Trial of Single Agent Ipilimumab (Anti-CTLA-4) for Locally Advanced or Metastatic Pancreatic Adenocarcinoma

(2010) Richard E. Royal et al.   JOURNAL OF IMMUNOTHERAPY

Covalent Modifiers: An Orthogonal Approach to Drug Design

(2009) Michele H. Potashman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Many faces of Ras activation

(2008) László Buday et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER