Science in Focus: Combining Radiotherapy with Inhibitors of the DNA Damage Response

Chalmers, Anthony J.

doi:10.1016/j.clon.2016.01.035

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…In addition to DDR modulator monotherapy treatments, of which efficacy mainly depends on synthetic lethal relationships with cancer-specific DDR mutations, combinations with other DNA damage-inducing therapies are actively being investigated [1]. Currently most data on DDR modulator combination regimens is available for PARP inhibitors, but other compounds such as ATR inhibitors are gaining increasing attention [136]. An important condition for these combination therapies is that the DDR modulator impairs a pathway involved in repair of the induced DNA damage by radiotherapy or chemotherapy, thereby leading to damage persistence and increase of cell death.…”

Section: Ddr Modulator Combinationsmentioning

confidence: 99%

DNA Damage-Inducing Anticancer Therapies: From Global to Precision Damage

Reuvers

Kanaar

Nonnekens

2020

Cancers

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DNA damage-inducing therapies are of tremendous value for cancer treatment and function by the direct or indirect formation of DNA lesions and subsequent inhibition of cellular proliferation. Of central importance in the cellular response to therapy-induced DNA damage is the DNA damage response (DDR), a protein network guiding both DNA damage repair and the induction of cancer-eradicating mechanisms such as apoptosis. A detailed understanding of DNA damage induction and the DDR has greatly improved our knowledge of the classical DNA damage-inducing therapies, radiotherapy and cytotoxic chemotherapy, and has paved the way for rational improvement of these treatments. Moreover, compounds targeting specific DDR proteins, selectively impairing DNA damage repair in cancer cells, form a promising novel therapy class that is now entering the clinic. In this review, we give an overview of the current state and ongoing developments, and discuss potential avenues for improvement for DNA damage-inducing therapies, with a central focus on the role of the DDR in therapy response, toxicity and resistance. Furthermore, we describe the relevance of using combination regimens containing DNA damage-inducing therapies and how they can be utilized to potentiate other anticancer strategies such as immunotherapy.

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Section: Ddr Modulator Combinationsmentioning

confidence: 99%

DNA Damage-Inducing Anticancer Therapies: From Global to Precision Damage

Reuvers

Kanaar

Nonnekens

2020

Cancers

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“…231 Examples of potential radiosensitising drugs with little independent antitumour efficacy are inhibitors of poly ADP-ribose polymerase, a DNA repair enzyme, and Wee-1, a cell cycle modulator. 232 …”

Section: Radiation Oncologymentioning

confidence: 99%

Future cancer research priorities in the USA: a Lancet Oncology Commission

Jaffee

Dang

Agus

et al. 2017

The Lancet Oncology

165

123

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We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.

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“…This notion is exemplified by the effectiveness of poly (ADP-ribose) polymerase (PARP) inhibitors in BRCA-deficient cells. This, alongside other advances in using DNA repair inhibitors for cancer treatment, is reviewed elsewhere [20,21]. Our review focuses on the implications of genomic instability as a whole on anticancer therapy.…”

Section: Cancer Treatmentmentioning

confidence: 99%