Muhammad Asad, Resident Radiation Oncology at Institute of Nuclear Medicine And Oncology Lahore INMOL, shared a post on LinkedIn:
“Why do PARP inhibitors selectively kill BRCA-mutated cancer cells while sparing most normal cells?
This is one of the most elegant examples of translational oncology and the concept of synthetic lethality—a topic that often seems complicated until the underlying DNA repair mechanisms are understood.
In my latest educational lecture, I’ve tried to simplify PARP inhibitors from first principles to clinical practice, covering:
- How DNA damage occurs and the major repair pathways
- PARP-mediated repair of single-strand breaks (SSBs)
- BRCA1/2 homologous recombination repair (HRR) of double-strand breaks (DSBs)
- Mechanism of action of PARP inhibitors and PARP trapping
- Synthetic lethality and why normal cells are relatively spared
Beyond the basic science, the lecture also reviews the landmark clinical trials that established PARP inhibitors in routine oncology practice:
- Ovarian cancer: SOLO-1, PAOLA-1, PRIMA
- Breast cancer: OlympiA, OlympiAD, EMBRACA
- Pancreatic cancer: POLO
- Prostate cancer: PROfound, TRITON-2, PROPEL, MAGNITUDE, and TALAPRO
I also discuss:
- Current indications
- Drug selection
- Dosages
- Toxicities
- Resistance mechanisms
The session was designed with Radiation Oncology and Medical Oncology trainees in mind, particularly those preparing for FRCR, FCPS, MD, IMM, and board examinations, while keeping the concepts clinically relevant for everyday practice.
I’ve attached a short clip below, and the link to the full lecture is provided here.
I hope this resource contributes to making complex oncology concepts a little more approachable for trainees and colleagues.”
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