**Core Concept**
Pemetrexed, an antifolate medication, targets cells with rapidly dividing DNA, such as cancer cells. It works by inhibiting key enzymes involved in folate metabolism, which are crucial for DNA synthesis and repair.

**Why the Correct Answer is Right**
Pemetrexed's mechanism of action (MOA) involves the inhibition of three enzymes: thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). By inhibiting these enzymes, pemetrexed depletes the intracellular pools of reduced folates, which are necessary for DNA synthesis and repair. This leads to the accumulation of toxic metabolites, ultimately causing DNA damage and cell death.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because pemetrexed's MOA does not primarily involve the inhibition of tyrosine kinases, which are a different class of enzymes involved in cell signaling and proliferation.

**Option B:** This option is incorrect because pemetrexed does not primarily work by inducing apoptosis through the mitochondrial pathway. While pemetrexed may induce apoptosis in cancer cells, its primary mechanism involves the inhibition of folate metabolism enzymes.

**Option C:** This option is incorrect because pemetrexed does not primarily involve the inhibition of topoisomerase enzymes, which are involved in DNA replication and transcription.

**Clinical Pearl / High-Yield Fact**
Pemetrexed is commonly used in combination with other chemotherapeutic agents, such as cisplatin, to treat non-small cell lung cancer (NSCLC). Its efficacy is enhanced by the concurrent administration of folic acid and vitamin B12, which can help mitigate the side effects of folate depletion.

**Correct Answer:** D. Inhibition of thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase.