Triple Negative Breast Cancer (TNBC)

Random Notes

Treatement available for ovarian and breast cancer

The standard care for ovarian cancer — a combination of surgery and chemotherapy — has remained almost unchanged since the 1960s

Called poly(ADP-ribose) polymerase inhibitors — PARP inhibitors for short — the drugs work by blocking enzymes involved in DNA repair processes that cancer cells rely on as they multiply

PARP inhibitors were developed to fight cancers with BRCA mutations, which greatly increase a person’s risk of developing breast and ovarian cancer, but mounting evidence points to benefits in people without these mutations, too.

PARP inhibitors exploit a principle known as synthetic lethality, in which two defects become fatal to a cell when combined.

The drugs target PARP enzymes, which are responsible for initiating an important mechanism of repairing breaks in single strands of DNA.The inhibitors block this process, causing single-strand breaks to progress into double-strand breaks.

In most cells, another mechanism for fixing double-strand breaks, known as homologous recombination, can then step in and save the cell. However, in some cells this second line of defence is also impaired — a condition called homologous recombination deficiency (HRD)Around half of ovarian cancers exhibit HRD, and roughly one-fifth of those are due to mutations in the BRCA genes, which code for proteins involved in DNA repair1 . Put simply BRCA-mutant cells lack the ability to repair the damage done by PARP inhibitors

olaparib was first approved in 2014 soon after Rucaparib and niraparib The efficacy of these drugs is now well-established, improving the length of time people remain alive without their tumours growing (called progression-free survival) by around six months

Differences in the molecular characteristics of the drugs cannot be entirely ruled out. For instance, a 2020 laboratory study suggested that the molecular conformations of PARP inhibitors help to determine the PARP-trapping strength. However, this study’s findings predict that olaparib would be stronger than niraparib — the opposite pattern to the trials.

progression-free survival increased by around 70% in both cases

The ATHENA trial, testing rucaparib as a first-line maintenance treatment, is expected to reach primary completion by the end of 2024.

One drug for all

People with platinum-sensitive cancer seem to enjoy longer progression-free survival when receiving a second PARP inhibitor regardless of BRCA or HRD .status

Second research paper

Reversal effect of quercetin on talazoparib resistance in BRCA1 mutant triple negative breast cancer

PARP inhibitor drugs

• iniparib
• talozoparib,
• veliparib,
• rucaparib and
• niraparib

PARP inhibit -> BRACA is already mutated so it will not work -> cell aptosis

Quercetin is a polyphenolic flavonoidwidely found in many fruits (apple,blueberries, broccoli, grape,leek), vegetables, nuts, and red wine.

Quercetin exerts

• anti-inflammatory,
• anti-diabetic,
• anti-allergic,
• antiviral,
• anti-fungal and
• significant anti-carcinogenic activities.

It has been reported that quercetin has a potential anticancer effect in different cancer cell lines (breast, prostate, osteosarcoma, colon, gastric,esophageal, ovarian cancer and hepatocellular carcinoma) through the induction of apoptosisboth in vitro and in vivo [17-25].

whole method is given in this research paper

Three PARP inhibitors (olaparib, rucaparib, andniraparib) have now been approved by the FDA for patients with BRCA-mutated ovarian cancer

Keywords

HR Homologous recombination

MDR Multiple Drugs resistance

Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death or death of an organism.

PARP Poly (ADP-ribose) polymerase

BRACA1 / BRACA2 BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are genes that produce proteins that help repair damaged DNA

Prognosis Prognosis is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stable over time; expectations of quality of life, such as the ability to carry out daily activities; the potential for complications and associated health issues; and the likelihood of survival (including life expectancy).

relapse To return to a former state.