Rational combinations of targeted cancer therapies: background, advances and challenges

H **, L Wang, R Bernards - Nature Reviews Drug Discovery, 2023‏ - nature.com
Over the past two decades, elucidation of the genetic defects that underlie cancer has
resulted in a plethora of novel targeted cancer drugs. Although these agents can initially be …

Non-genetic mechanisms of therapeutic resistance in cancer

JC Marine, SJ Dawson, MA Dawson - Nature Reviews Cancer, 2020‏ - nature.com
Therapeutic resistance continues to be an indominable foe in our ambition for curative
cancer treatment. Recent insights into the molecular determinants of acquired treatment …

Pan-KRAS inhibitor disables oncogenic signalling and tumour growth

D Kim, L Herdeis, D Rudolph, Y Zhao, J Böttcher… - Nature, 2023‏ - nature.com
KRAS is one of the most commonly mutated proteins in cancer, and efforts to directly inhibit
its function have been continuing for decades. The most successful of these has been the …

Diverse alterations associated with resistance to KRAS (G12C) inhibition

Y Zhao, YR Murciano-Goroff, JY Xue, A Ang, J Lucas… - Nature, 2021‏ - nature.com
Inactive state-selective KRAS (G12C) inhibitors,,,,,,–demonstrate a 30–40% response rate
and result in approximately 6-month median progression-free survival in patients with lung …

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

ME Bahar, HJ Kim, DR Kim - Signal transduction and targeted therapy, 2023‏ - nature.com
Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality,
underscores the urgent need for enhanced insights into the molecular and cellular …

Genetic and non-genetic clonal diversity in cancer evolution

JRM Black, N McGranahan - Nature Reviews Cancer, 2021‏ - nature.com
The observation and analysis of intra-tumour heterogeneity (ITH), particularly in genomic
studies, has advanced our understanding of the evolutionary forces that shape cancer …

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

JY Xue, Y Zhao, J Aronowitz, TT Mai, A Vides, B Qeriqi… - Nature, 2020‏ - nature.com
KRAS GTPases are activated in one-third of cancers, and KRAS (G12C) is one of the most
common activating alterations in lung adenocarcinoma,. KRAS (G12C) inhibitors, are in …

Resolving genetic heterogeneity in cancer

S Turajlic, A Sottoriva, T Graham… - Nature Reviews Genetics, 2019‏ - nature.com
To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones
mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the …

Targeting the MAPK pathway in KRAS-driven tumors

M Drosten, M Barbacid - Cancer cell, 2020‏ - cell.com
KRAS mutations occur in a quarter of all of human cancers, yet no selective drug has been
approved to treat these tumors. Despite the recent development of drugs that block KRAS …

Targeting alterations in the RAF–MEK pathway

R Yaeger, RB Corcoran - Cancer discovery, 2019‏ - AACR
The MAPK pathway is one of the most commonly mutated oncogenic pathways in cancer.
Although RAS mutations are the most frequent MAPK alterations, less frequent alterations in …